Mitochondrial oxidative phosphorylation (OXPHOS) is central to physiology and disease pathogenesis. To systematically investigate its activity and regulation, we performed a wide range of assays of OXPHOS physiology and nuclear and mitochondrial gene expression across 2490 chemical perturbations in muscle cells. Through mining of the resulting compendium, we discovered that: ... More
Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.
AuthorsHu T, Ramachandrarao SP, Siva S, Valancius C, Zhu Y, Mahadev K, Toh I, Goldstein BJ, Woolkalis M, Sharma K
JournalAm J Physiol Renal Physiol
PubMed ID16159901
'Cytoskeletal alterations in endothelial cells have been linked to nitric oxide generation and cell-cell interactions. Transforming growth factor (TGF)-beta has been described to affect cytoskeletal rearrangement in numerous cell types; however, the underlying pathway is unclear. In the present study, we found that human umbilical vein endothelial cells (HUVEC) have ... More
The yeast prion Ure2p native-like assemblies are toxic to mammalian cells regardless of their aggregation state.
AuthorsPieri L, Bucciantini M, Nosi D, Formigli L, Savistchenko J, Melki R, Stefani M
JournalJ Biol Chem
PubMed ID16571726
'The yeast prion Ure2p assembles in vitro into oligomers and fibrils retaining the alpha-helix content and binding properties of the soluble protein. Here we show that the different forms of Ure2p native-like assemblies (dimers, oligomers, and fibrils) are similarly toxic to murine H-END cells when added to the culture medium. ... More
Role of extracellular signal-regulated protein kinase in neuronal cell death induced by glutathione depletion in neuron/glia mesencephalic cultures.
Authorsde Bernardo S, Canals S, Casarejos MJ, Solano RM, Menendez J, Mena MA
JournalJ Neurochem
PubMed ID15485497
'To date, glutathione (GSH) depletion is the earliest biochemical alteration shown in brains of Parkinson''s disease patients, but the role of GSH in dopamine cell survival is debated. In this study we show that GSH depletion, produced with GSH synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO), induces selectively neuronal cell death in neuron/glia, ... More
Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells.
AuthorsYalcin S, Zhang X, Luciano JP, Mungamuri SK, Marinkovic D, Vercherat C, Sarkar A, Grisotto M, Taneja R, Ghaffari S,
JournalJ Biol Chem
PubMed ID18424439
'Unchecked accumulation of reactive oxygen species (ROS) compromises maintenance of hematopoietic stem cells. Regulation of ROS by the tumor suppressor protein ataxia telangiectasia mutated (ATM) is critical for preserving the hematopoietic stem cell pool. In this study we demonstrate that the Foxo3 member of the Forkhead Box O (FoxO) family ... More
Circulating white blood cells and platelets amplify oxidative stress in heart failure.
AuthorsIjsselmuiden AJ, Musters RJ, de Ruiter G, van Heerebeek L, Alderse-Baas F, van Schilfgaarde M, Leyte A, Tangelder GJ, Laarman GJ, Paulus WJ,
JournalNat Clin Pract Cardiovasc Med
PubMed ID18957960
'BACKGROUND: Mitochondria of circulating white blood cells (WBC) and platelets sense oxidative stress during capillary passage and react by producing reactive oxygen species (ROS). Although evidence indicates that congestive heart failure (CHF) is associated with oxidative stress, the role of WBC and platelets as mediators in CHF has not been ... More
High glucose induces adipogenic differentiation of muscle-derived stem cells.
AuthorsAguiari P, Leo S, Zavan B, Vindigni V, Rimessi A, Bianchi K, Franzin C, Cortivo R, Rossato M, Vettor R, Abatangelo G, Pozzan T, Pinton P, Rizzuto R,
JournalProc Natl Acad Sci U S A
PubMed ID18212116
'Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ... More
IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress.
AuthorsKajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P
JournalDiabetes
PubMed ID11375343
'Stimulation of the local renin-angiotensin system and apoptosis characterize the diabetic heart. Because IGF-1 reduces angiotensin (Ang) II and apoptosis, we tested whether streptozotocin-induced diabetic cardiomyopathy was attenuated in IGF-1 transgenic mice (TGM). Diabetes progressively depressed ventricular performance in wild-type mice (WTM) but had no hemodynamic effect on TGM. Myocyte ... More
Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.
AuthorsJeng JH, Wang YJ, Chang WH, Wu HL, Li CH, Uang BJ, Kang JJ, Lee JJ, Hahn LJ, Lin BR, Chang MC
JournalCell Mol Life Sci
PubMed ID14704856
'Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is ... More
Fatty acid amide hydrolase determines anandamide-induced cell death in the liver.
AuthorsSiegmund SV, Seki E, Osawa Y, Uchinami H, Cravatt BF, Schwabe RF
JournalJ Biol Chem
PubMed ID16418162
'The endocannabinoid anandamide (AEA) induces cell death in many cell types, but determinants of AEA-induced cell death remain unknown. In this study, we investigated the role of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH) in AEA-induced cell death in the liver. Primary hepatocytes expressed high levels of FAAH and ... More
Ouabain interaction with cardiac Na+/K+-ATPase initiates signal cascades independent of changes in intracellular Na+ and Ca2+ concentrations.
AuthorsLiu J, Tian J, Haas M, Shapiro JI, Askari A, Xie Z
JournalJ Biol Chem
PubMed ID10874029
'We have shown previously that partial inhibition of the cardiac myocyte Na(+)/K(+)-ATPase activates signal pathways that regulate myocyte growth and growth-related genes and that increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and reactive oxygen species (ROS) are two essential second messengers within these pathways. The aim of this work was to ... More
Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species.
AuthorsXu A, Zhou H, Yu DZ, Hei TK
JournalEnviron Health Perspect
PubMed ID12361925
'Asbestos is an important environmental carcinogen in the United States and remains the primary occupational concern in many developing countries; however, the underlying mechanisms of its genotoxicity are not known. We showed previously that asbestos is a potent gene and chromosomal mutagen in mammalian cells and that it induces mostly ... More
Role of glutathione in determining the differential sensitivity between the cortical and cerebellar regions towards mercury-induced oxidative stress.
AuthorsKaur P, Aschner M, Syversen T
JournalToxicology
PubMed ID17169475
'Certain discrete areas of the CNS exhibit enhanced sensitivity towards MeHg. To determine whether GSH is responsible for this particular sensitivity, we investigated its role in MeHg-induced oxidative insult in primary neuronal and astroglial cell cultures of both cerebellar and cortical origins. For this purpose, ROS and GSH were measured ... More
AuthorsYamagishi S, Nakamura K, Matsui T, Inagaki Y, Takenaka K, Jinnouchi Y, Yoshida Y, Matsuura T, Narama I, Motomiya Y, Takeuchi M, Inoue H, Yoshimura A, Bucala R, Imaizumi T
JournalJ Biol Chem
PubMed ID16707486
'Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis, suggesting that loss of PEDF contributes to proliferative diabetic retinopathy. However, the role of PEDF against retinal vascular hyperpermeability remains to be elucidated. We investigated here whether and how PEDF could inhibit the advanced glycation end product (AGE) signaling ... More
Decreasing cellular hydrogen peroxide with catalase mimics the effects of hypoxia on the sensitivity of the L-type Ca2+ channel to beta-adrenergic receptor stimulation in cardiac myocytes.
AuthorsHool LC, Arthur PG
JournalCirc Res
PubMed ID12364388
'In cardiac myocytes, hypoxia inhibits the basal L-type Ca2+ current (I(Ca-L)) and increases the sensitivity of I(Ca-L) to beta-adrenergic receptor stimulation. We investigated whether hydrogen peroxide (H2O2) is involved in the hypoxic response. Guinea pig ventricular myocytes were dialyzed with catalase, which specifically catalyzes the conversion of H2O2 to H2O ... More
NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-alpha.
AuthorsGertzberg N, Neumann P, Rizzo V, Johnson A
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID12807699
'We tested the hypothesis that the NAD(P)H oxidase-dependent generation of superoxide anion (O2-*) mediates tumor necrosis factor-alpha (TNF)-induced alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The NAD(P)H oxidase subcomponents p47phox and p22phox were ... More
Accurate measure of laser irradiance threshold for near-infrared photo-oxidation with a modified confocal microscope.
AuthorsDenton ML, Schuster KJ, Rockwell BA
JournalJ Microsc
PubMed ID16551277
'Femtosecond mode-locked lasers are now being used routinely in multiphoton fluorescence and autofluorescence spectroscopy, are just beginning to be used in refractive surgery, and may be used in the future diagnosis of skin cancer. Pulses from these lasers induce non-linear effects in resultant tissue interactions. Using a modified confocal microscope ... More
Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death.
AuthorsMishra DP, Pal R, Shaha C
JournalJ Biol Chem
PubMed ID16301318
'Bcl-x exists in two isoforms, the anti-apoptotic form Bcl-xL and the proapoptotic form Bcl-xS. The critical balance between the two forms appears to be important for cell survival; however, it is still not clear exactly how the vital balance is maintained. Using an in vitro spermatogenic cell apoptosis model, this ... More
Evidence for redox regulation of cytochrome C release during programmed neuronal death: antioxidant effects of protein synthesis and caspase inhibition.
AuthorsKirkland RA, Franklin JL,
JournalJ Neurosci
PubMed ID11245680
'Sympathetic neurons die by apoptosis when they are deprived of nerve growth factor (NGF). Activation of caspases by cytochrome c released from mitochondria is central to this death. In this report we present evidence that cellular redox state regulates cytochrome c redistribution in these neurons. An increase of mitochondrial-produced reactive ... More
Glutamate loading protects freshly isolated and perfused adult cardiomyocytes against intracellular ROS generation.
AuthorsKing N, McGivan JD, Griffiths EJ, Halestrap AP, Suleiman MS
JournalJ Mol Cell Cardiol
PubMed ID12878484
'Glutamate loading has been shown to protect single isolated perfused cardiomyocytes against metabolic inhibition and wash-off. The mechanism underpinning this protection is unknown. This study aimed to investigate whether reactive oxygen species (ROS) are generated by single isolated perfused cardiomyocytes and whether the protective effect of glutamate loading on cell ... More
Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes.
AuthorsBienert GP, Møller AL, Kristiansen KA, Schulz A, Møller IM, Schjoerring JK, Jahn TP
JournalJ Biol Chem
PubMed ID17105724
'The metabolism of aerobic organisms continuously produces reactive oxygen species. Although potentially toxic, these compounds also function in signaling. One important feature of signaling compounds is their ability to move between different compartments, e.g. to cross membranes. Here we present evidence that aquaporins can channel hydrogen peroxide (H2O2). Twenty-four aquaporins ... More
Combination of 5-fluorouracil and N1,N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells.
AuthorsChoi W, Gerner EW, Ramdas L, Dupart J, Carew J, Proctor L, Huang P, Zhang W, Hamilton SR
JournalJ Biol Chem
PubMed ID15546879
'The thymidylate synthase inhibitor 5-fluorouracil (5-FU) is used widely for chemotherapy of colorectal carcinoma. Recent studies showed that 5-FU affects polyamine metabolism in colon carcinoma cells. We therefore examined whether combinations of 5-FU with drugs that specifically target polyamine metabolism, i.e. N1,N11-diethylnorspermine (DENSPM) or alpha-difluoromethylornithine (DFMO), have synergistic effects in ... More
Characteristics and function of cardiac mitochondrial nitric oxide synthase.
AuthorsDedkova EN, Blatter LA,
JournalJ Physiol
PubMed ID19103678
'We used laser scanning confocal microscopy in combination with the nitric oxide (NO)-sensitive fluorescent dye DAF-2 and the reactive oxygen species (ROS)-sensitive dyes CM-H(2)DCF and MitoSOX Red to characterize NO and ROS production by mitochondrial NO synthase (mtNOS) in permeabilized cat ventricular myocytes. Stimulation of mitochondrial Ca(2+) uptake by exposure ... More
Time to fatigue is increased in mouse muscle at 37 degrees C; the role of iron and reactive oxygen species.
AuthorsReardon TF, Allen DG,
JournalJ Physiol
PubMed ID19470779
'Studies exploring the rate of fatigue in isolated muscle at 37 degrees C have produced mixed results. In the present study, muscle fibre bundles from the mouse foot were used to study the effect of temperature on the rate of muscle fatigue. Provided iron was excluded from the solutions, time ... More
Alterations of cellular redox state during NNK-induced malignant transformation and resistance to radiation.
AuthorsDemizu Y, Sasaki R, Trachootham D, Pelicano H, Colacino JA, Liu J, Huang P,
JournalAntioxid Redox Signal
PubMed ID18257743
'Cancer cells often exhibit increased reactive oxygen species generation and altered redox regulation. The current study was conducted to investigate the biochemical and molecular events associated with redox alterations during chemical-induced malignant transformation and to evaluate their potential roles in radiation sensitivity. Immortalized nonmalignant human bronchial epithelial cells were exposed ... More
Contribution of persistent C-Jun N-terminal kinase activity to the survival of human vestibular schwannoma cells by suppression of accumulation of mitochondrial superoxides.
AuthorsYue WY, Clark JJ, Fernando A, Domann F, Hansen MR,
JournalNeuro Oncol
PubMed ID21697181
'Vestibular schwannomas (VSs) result from inactivating mutations in the merlin tumor suppressor gene. The merlin protein suppresses a variety of progrowth kinase-signaling cascades, including extracellular regulated kinase/mitogen-activated protein kinase (ERK/MAPK), c-Jun N-terminal kinase (JNK), and phosphatidyl-inositol 3-kinase (PI3-K)/Akt. Recent studies indicate that ERKs and Akt are active in human VSs, ... More
Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases.
AuthorsKirkland RA, Saavedra GM, Cummings BS, Franklin JL,
JournalJ Neurosci
PubMed ID21123558
'A Bax- and, apparently, mitochondria-dependent increase in superoxide (O(2)(·-)) and other reactive oxygen species (ROS) occurs in apoptotic superior cervical ganglion (SCG) and cerebellar granule (CG) neurons. Here we show that Bax also lies upstream of ROS produced in nonapoptotic neurons and present evidence that caspases partially mediate the pro-oxidant ... More
Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation.
AuthorsDu X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M
JournalJ Clin Invest
PubMed ID16528409
'Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of ... More
Azathioprine and UVA light generate mutagenic oxidative DNA damage.
AuthorsO'Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P
JournalScience
PubMed ID16166520
'Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of therapy-related cancer. We suggest that immunosuppression by azathioprine (Aza) may be one such treatment. Aza causes the accumulation of 6-thioguanine (6-TG) ... More
Spatial control of reactive oxygen species formation in fibroblasts using two-photon excitation.
AuthorsKing BA, Oh DH
JournalPhotochem Photobiol
PubMed ID15339206
'Two-photon excitation (2PE) provides a means of generating reactive oxygen species (ROS) in cells and tissues with a high degree of spatial specificity. In cultured monolayers of human fibroblasts and fibroblast-derived cells treated with the commonly used probe of ROS formation, 5-(and 6)-chloromethyl-2'',7''-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H(2)DCFDA), cells irradiated through ... More
Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission.
AuthorsMatarrese P, Tinari A, Mormone E, Bianco GA, Toscano MA, Ascione B, Rabinovich GA, Malorni W
JournalJ Biol Chem
PubMed ID15556941
'Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, ... More
Persistent oxidative stress in chromosomally unstable cells.
AuthorsLimoli CL, Giedzinski E, Morgan WF, Swarts SG, Jones GD, Hyun W
JournalCancer Res
PubMed ID12810636
'Past work using the human-hamster hybrid line GM10115 has demonstrated that exposure to a variety of DNA damaging agents can lead to the persistent destabilization of chromosomes. To gain insight into the potential biochemical mechanisms involved in perpetuating the unstable phenotype, groups of clones characterized as stable or unstable were ... More
Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.
AuthorsRo SH, Nam M, Jang I, Park HW, Park H, Semple IA, Kim M, Kim JS, Park H, Einat P, Damari G, Golikov M, Feinstein E, Lee JH,
Journal
PubMed ID24825887
'Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in ... More
Rapid activation of antioxidant defenses by nerve growth factor suppresses reactive oxygen species during neuronal apoptosis: evidence for a role in cytochrome c redistribution.
AuthorsKirkland RA, Saavedra GM, Franklin JL,
JournalJ Neurosci
PubMed ID17942726
'Depriving mouse sympathetic neurons of nerve growth factor (NGF) causes their apoptotic death. A Bax-dependent increase of mitochondrial-derived reactive oxygen species (ROS) begins in these cells soon after NGF withdrawal. We investigated the effects on these ROS of adding NGF to cultures of NGF-deprived neurons. ROS levels were monitored with ... More
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.
AuthorsNishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M
JournalNature
PubMed ID10783895
'Diabetic hyperglycaemia causes a variety of pathological changes in small vessels, arteries and peripheral nerves. Vascular endothelial cells are an important target of hyperglycaemic damage, but the mechanisms underlying this damage are not fully understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase ... More
Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity.
AuthorsLiu SX, Athar M, Lippai I, Waldren C, Hei TK
JournalProc Natl Acad Sci U S A
PubMed ID11172004
'Although arsenic is a well-established human carcinogen, the mechanisms by which it induces cancer remain poorly understood. We previously showed arsenite to be a potent mutagen in human-hamster hybrid (A(L)) cells, and that it induces predominantly multilocus deletions. We show here by confocal scanning microscopy with the fluorescent probe 5'',6''-chloromethyl-2'',7''-dichlorodihydrofluorescein ... More
Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein.
AuthorsSung JY, Kim J, Paik SR, Park JH, Ahn YS, Chung KC
JournalJ Biol Chem
PubMed ID11316809
'The presynaptic alpha-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson''s disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer''s disease. Here we examined the pathogenic mechanism of neuronal cell death induced by alpha-synuclein. The exogenous addition of alpha-synuclein ... More
In situ detection and measurement of intracellular reactive oxygen species in single isolated mature skeletal muscle fibers by real time fluorescence microscopy.
AuthorsPalomero J, Pye D, Kabayo T, Spiller DG, Jackson MJ,
JournalAntioxid Redox Signal
PubMed ID18407749
'Reactive oxygen species (ROS) produced by skeletal muscle stimulate adaptive responses to activity and mediate some degenerative processes. ROS activity is usually studied by measuring indirect end-points of their reactions with various biomolecules. In order to develop a method to measure the intracellular ROS generation in real-time in mature skeletal ... More
The use of fluorescence for detecting MeHg-induced ROS in cell cultures.
AuthorsKaur P, Schulz K, Heggland I, Aschner M, Syversen T,
JournalToxicol In Vitro
PubMed ID18343630
'The effect of methylmercury (MeHg) on reactive oxygen species (ROS) induction in neural cell lines was measured by the fluorescent probe, chloro methyl derivative of di-chloro di-hydro fluoresceindiacetate (CMH(2)DCFDA). Three different MeHg concentrations (5, 10 and 25muM) and time periods (30, 50 and 90min) were studied in C6-glial and B35-neuronal ... More
OXIDANT-INJURED AIRWAY EPITHELIAL CELLS UPREGULATE THIOREDOXIN BUT DO NOT PRODUCE IL-8.
Exposure to estrogens increases the risk of breast and endometrial cancer. It is proposed that the estrogen receptor (ER) may contribute to estrogen carcinogenesis by transduction of the hormonal signal and as a ... More
Mitochondrial transfer between cells can rescue aerobic respiration.
AuthorsSpees JL, Olson SD, Whitney MJ, Prockop DJ
JournalProc Natl Acad Sci U S A
PubMed ID16432190
Current theory indicates that mitochondria were obtained 1.5 billion years ago from an ancient prokaryote. The mitochondria provided the capacity for aerobic respiration, the creation of the eukaryotic cell, and eventually complex multicellular organisms. Recent reports have found that mitochondria play essential roles in aging and determining lifespan. A variety ... More
JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.
AuthorsVentura JJ, Cogswell P, Flavell RA, Baldwin AS, Davis RJ
JournalGenes Dev
PubMed ID15545623
The c-Jun NH(2)-terminal kinase (JNK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of JNK in tumor necrosis factor (TNF)-stimulated cell death using fibroblasts isolated from wild-type, Mkk4(-/-) Mkk7(-/-), and Jnk1(-/-) Jnk2(-/-) mice. We demonstrate that JNK can act to ... More
Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects.
AuthorsWardman P,
JournalFree Radic Biol Med
PubMed ID17761297
Chemical probes for free radicals in biology are important tools; fluorescence and chemiluminescence offer high detection sensitivity. This article reviews progress in the development of probes for "reactive oxygen and nitrogen" species, emphasizing the caution needed in their use. Reactive species include hydrogen peroxide; hydroxyl, superoxide, and thiyl radicals; carbonate ... More
Parkinson's disease-associated human ATP13A2 (PARK9) deficiency causes zinc dyshomeostasis and mitochondrial dysfunction.
AuthorsPark JS, Koentjoro B, Veivers D, Mackay-Sim A, Sue CM,
Journal
PubMed ID24399444
Human ATP13A2 (PARK9), a lysosomal type 5 P-type ATPase, has been associated with autosomal recessive early-onset Parkinson's disease (PD). ATP13A2 encodes a protein that is highly expressed in neurons and is predicted to function as a cation pump, although the substrate specificity remains unclear. Accumulation of zinc and mitochondrial dysfunction ... More
Photoactivation of Endogenous Latent Transforming Growth Factor-ß1 Directs Dental Stem Cell Differentiation for Regeneration.
AuthorsArany PR, Cho A, Hunt TD, Sidhu G, Shin K, Hahm E, Huang GX, Weaver J, Chen AC, Padwa BL, Hamblin MR, Barcellos-Hoff MH, Kulkarni AB, J Mooney D,
Journal
PubMed ID24871130
Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even ... More
Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury.
AuthorsZhang Y, Sauler M, Shinn AS, Gong H, Haslip M, Shan P, Mannam P, Lee PJ,
Journal
PubMed ID24778451
High levels of inspired oxygen, hyperoxia, are frequently used in patients with acute respiratory failure. Hyperoxia can exacerbate acute respiratory failure, which has high mortality and no specific therapies. We identified novel roles for PTEN-induced putative kinase 1 (PINK1), a mitochondrial protein, and the cytosolic innate immune protein NLRP3 in ... More
Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy.
AuthorsShi Y, Han JJ, Tennakoon JB, Mehta FF, Merchant FA, Burns AR, Howe MK, McDonnell DP, Frigo DE,
JournalMol Endocrinol
PubMed ID23250485
Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases. However, the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood. In this study, we have determined that androgens regulate overall cell metabolism and cell growth, in part, by increasing ... More
ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1.
AuthorsIlatovskaya DV, Pavlov TS, Levchenko V, Staruschenko A,
JournalAm J Physiol Cell Physiol
PubMed ID23135700
The epithelial Na(+) channel (ENaC) is a key transporter participating in the fine tuning of Na(+) reabsorption in the nephron. ENaC activity is acutely upregulated by epidermal growth factor (EGF), insulin, and insulin-like growth factor-1 (IGF-1). It was also proposed that reactive oxygen species (ROS) have a stimulatory effect on ... More
Indoxyl sulfate induces complex redox alterations in mesangial cells.
AuthorsGelasco AK, Raymond JR,
JournalAm J Physiol Renal Physiol
PubMed ID16434574
Indoxyl sulfate is a protein metabolite that is concentrated in the serum of patients with chronic renal insufficiency. It also is a uremic toxin that has been implicated in the progression of chronic renal disease in rodent models. We have shown previously that mesangial cell redox status is related to ... More
A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation.
AuthorsLin X, David CA, Donnelly JB, Michaelides M, Chandel NS, Huang X, Warrior U, Weinberg F, Tormos KV, Fesik SW, Shen Y,
JournalProc Natl Acad Sci U S A
PubMed ID18172210
Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development and progression by regulating genes that are vital for proliferation, glycolysis, angiogenesis, and metastasis. To identify strategies of targeting the HIF-1 pathway, we screened a siRNA library against the entire druggable genome and a small-molecule library consisting of 691,200 compounds ... More
Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes.
AuthorsOlmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, Monsalve M,
JournalJ Biol Chem
PubMed ID19324885
Oxidative stress is a hallmark of metabolism-related diseases and a risk factor for atherosclerosis. FoxO factors have been shown to play a key role in vascular endothelial development and homeostasis. Foxo3a can protect quiescent cells from oxidative stress through the regulation of detoxification genes such as sod2 and catalase. Here ... More
Superoxide dismutase 1 regulates caspase-1 and endotoxic shock.
AuthorsMeissner F, Molawi K, Zychlinsky A,
JournalNat Immunol
PubMed ID18604212
Caspase-1 serves an essential function in the initiation of inflammation by proteolytically maturing the cytokines interleukin 1 beta and interleukin 18. Several Nod-like receptors activate caspase-1 in response to microbial and 'danger' signals by assembling cytosolic protein complexes called 'inflammasomes'. We show here that superoxide dismutase 1 (SOD1) regulates caspase-1 ... More
The effect of oxidative stress on Ca2+ release and capacitative Ca2+ entry in vascular endothelial cells.
AuthorsFlorea SM, Blatter LA,
JournalCell Calcium
PubMed ID17767954
Oxidative stress imposed by the accumulation of oxygen free radicals (reactive oxygen species, ROS) has profound effects on Ca2+ homeostasis in the vascular endothelium, leading to endothelial dysfunctions and the development of cardiovascular pathologies. We tested the effect of the oxidant and ROS generator tert-butyl-hydroperoxide (tBuOOH) on Ca2+ signaling in ... More
Identification of ROS using oxidized DCFDA and flow-cytometry.
AuthorsEruslanov E, Kusmartsev S,
JournalMethods Mol Biol
PubMed ID20072909
Cells constantly generate reactive oxygen species (ROS) during aerobic metabolism. The ROS generation plays an important protective and functional role in the immune system. The cell is armed with a powerful antioxidant defense system to combat excessive production of ROS. Oxidative stress occurs in cells when the generation of ROS ... More
Amplification of CD95 activation by caspase 8-induced endosomal acidification in rat hepatocytes.
AuthorsReinehr R, Sommerfeld A, Keitel V, Grether-Beck S, Haüssinger D,
JournalJ Biol Chem
PubMed ID18045865
Although in rat hepatocytes CD95 is predominantly located inside the cell with almost undetectable immunostaining at the plasma membrane, the addition of CD95-ligand (CD95L) induces hepatocyte apoptosis, which is preceded by a targeting and activation of intracellularly localized CD95 to the plasma membrane including formation of the death-inducing signaling complex. ... More
Reactive Oxygen Species-Activated Akt/ASK1/p38 Signaling Pathway in Nickel Compound-Induced Apoptosis in BEAS 2B Cells.
AuthorsPan J, Chang Q, Wang X, Son Y, Zhang Z, Chen G, Luo J, Bi Y, Chen F, Shi X,
JournalChem Res Toxicol
PubMed ID20112989
Nickel compounds are carcinogenic to humans, possibly through induction of reactive oxygen species (ROS) that damage macromolecules including DNA and proteins. The aim of the present study is to elucidate the role of the ROS-mediated Akt/apoptosis-regulating signal kinase (ASK) 1/p38 pathway in nickel-induced apoptosis. Exposure of human bronchial epithelial cells ... More
Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species (ROS) generation by mitochondria and the NADPH oxidase, Nox4, in mesangial cells.
AuthorsShah A, Xia L, Goldberg H, Lee KW, Quaggin SE, Fantus IG,
JournalJ Biol Chem
PubMed ID23329835
Objective: Thioredoxin-interacting protein (TxNIP) is upregulated by high glucose and is associated with oxidative stress. It has been implicated in hyperglycemia-induced beta-cell dysfunction and apoptosis. As high glucose and oxidative stress mediate diabetic nephropathy (DN), the contribution of TxNIP was investigated in renal mesangial cell reactive oxygen species (ROS) generation ... More
In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone.
AuthorsDykens JA, Jamieson JD, Marroquin LD, Nadanaciva S, Xu JJ, Dunn MC, Smith AR, Will Y,
JournalToxicol Sci
PubMed ID18344530
Mitochondrial toxicity is increasingly implicated in a host of drug-induced organ toxicities, including hepatotoxicity. Nefazodone was withdrawn from the U.S. market in 2004 due to hepatotoxicity. Accordingly, we evaluated nefazodone, another triazolopyridine trazodone, plus the azaspirodecanedione buspirone, for cytotoxicity and effects on mitochondrial function. In accord with its clinical disposition, ... More
Enhanced mitochondrial superoxide in hyperglycemic endothelial cells: direct measurements and formation of hydrogen peroxide and peroxynitrite.
AuthorsQuijano C, Castro L, Peluffo G, Valez V, Radi R,
JournalAm J Physiol Heart Circ Physiol
PubMed ID17906108
Hyperglycemic challenge to bovine aortic endothelial cells (BAECs) increases oxidant formation and cell damage that are abolished by MnSOD overexpression, implying mitochondrial superoxide (O(2)(.-)) as a central mediator. However, mitochondrial O(2)(.-) and its steady-state concentrations have not been measured directly yet. Therefore, we aimed to detect and quantify O(2)(.-) through ... More
H(2)O(2)-mediated modulation of cytosolic signaling and organelle function in rat hippocampus.
AuthorsGerich FJ, Funke F, Hildebrandt B, Fasshauer M, Müller M,
JournalPflugers Arch
PubMed ID19430810
Reactive oxygen species (ROS) released from (dys-)functioning mitochondria contribute to normal and pathophysiological cellular signaling by modulating cytosolic redox state and redox-sensitive proteins. To identify putative redox targets involved in such signaling, we exposed hippocampal neurons to hydrogen peroxide (H(2)O(2)). Redox-sensitive dyes indicated that externally applied H(2)O(2) may oxidize intracellular ... More
Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease.
AuthorsQuintanilla RA, Jin YN, Fuenzalida K, Bronfman M, Johnson GV,
JournalJ Biol Chem
PubMed ID18640979
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the PPAR family of transcription factors. Synthetic PPARgamma agonists are used as oral anti-hyperglycemic drugs for the treatment of non-insulin-dependent diabetes. However, emerging evidence indicates that PPARgamma activators can also prevent or attenuate neurodegeneration. Given these previous findings, the focus of this ... More
TRPM7 activates m-calpain by stress-dependent stimulation of p38 MAPK and c-Jun N-terminal kinase.
TRPM7 is a Ca(2)(+)-permeant and Mg(2)(+)-permeant ion channel in possession of its own kinase domain. In a previous study, we showed that overexpression of the channel-kinase in HEK-293 cells produced cell rounding and loss of adhesion, which was dependent on the Ca(2+)-dependent protease m-calpain. The TRPM7-elicited change in cell morphology ... More
Illumination of the malaria parasite Plasmodium falciparum alters intracellular pH. Implications for live cell imaging.
AuthorsWissing F, Sanchez CP, Rohrbach P, Ricken S, Lanzer M,
JournalJ Biol Chem
PubMed ID12140286
Live cell fluorescence microscopy has been widely used to study physiological processes in the human malarial parasite Plasmodium falciparum, including pH homeostasis, Ca(2+) signaling and protein targeting. However, the reproducibility of the data is often poor. Controversial statements exist regarding cytosolic and vacuolar baseline pH, as well as regarding the ... More
Hypoxia-inducible factor-1alpha, a key factor in the keratinocyte response to UVB exposure.
AuthorsRezvani HR, Dedieu S, North S, Belloc F, Rossignol R, Letellier T, de Verneuil H, Taïeb A, Mazurier F
JournalJ Biol Chem
PubMed ID17400550
Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor sensitive to oxygen levels, which responds to stress factors under both hypoxic and nonhypoxic conditions. UV irradiation being a common stressor of skin, we looked at the effect of UVB on HIF-1alpha expression in keratinocytes. We found that UVB induces a biphasic ... More
Requirement of Rac1 in the development of cardiac hypertrophy.
AuthorsSatoh M, Ogita H, Takeshita K, Mukai Y, Kwiatkowski DJ, Liao JK
JournalProc Natl Acad Sci U S A
PubMed ID16651530
The development of cardiac hypertrophy is mediated, in part, by increase in NADPH oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in which "phox" is phagocyte oxidase). However, it is not known which Rac isoform mediates this effect ... More
The plasma membrane Na+/H+ antiporter SOS1 interacts with RCD1 and functions in oxidative stress tolerance in Arabidopsis.
AuthorsKatiyar-Agarwal S, Zhu J, Kim K, Agarwal M, Fu X, Huang A, Zhu JK
JournalProc Natl Acad Sci U S A
PubMed ID17023541
The adverse effects of high salt on plants include Na(+) toxicity and hyperosmotic and oxidative stresses. The plasma membrane-localized Na(+)/H(+) antiporter SOS1 functions in the extrusion of toxic Na(+) from cells and is essential for plant salt tolerance. We report here that, under salt or oxidative stress, SOS1 interacts through ... More
Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate cytokines.
AuthorsLv W, Zhang M, Zhang Z, Huang L, Yang S, Yin L, Hong J, Han D, Chen C, Vidyasagar S, Okunieff P, Zhang L
Journal
PubMed ID23852495
Amifostine is a first-line cytoprotective drug used to prevent radiotherapy-induced or chemotherapy-induced injuries. However, its mechanism of action is not well understood. In this study, freshly harvested bone marrow cells were treated with amifostine and analyzed with a series of mitochondrial indices. In vitro results showed that bone marrow cells ... More
Hydrogen peroxide mediates plant root cell response to nutrient deprivation.
AuthorsShin R, Schachtman DP
JournalProc Natl Acad Sci U S A
PubMed ID15173595
Potassium (K(+)) is an essential nutrient required by plants in large quantities, but changes in soil concentrations may limit K(+) acquisition by roots. It is not known how plant root cells sense or signal the changes that occur after the onset of K(+) deficiency. Changes in the kinetics of Rb(+) ... More
Reactive oxygen species derived from the mitochondrial respiratory chain are not responsible for the basal levels of oxidative base modifications observed in nuclear DNA of Mammalian cells.
The mitochondrial electron transport chain (ETC) is the most important source of reactive oxygen species (ROS) in mammalian cells. To assess its relevance to the endogenous generation of oxidative DNA damage in the nucleus, we have compared the background (steady-state) levels of oxidative DNA base modifications sensitive to the repair ... More
Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes.
AuthorsRezvani HR, Mazurier F, Cario-André M, Pain C, Ged C, Taïeb A, de Verneuil H
JournalJ Biol Chem
PubMed ID16644728
UV-induced apoptosis in keratinocytes is a highly complex process in which various molecular pathways are involved. These include the extrinsic pathway via triggering of death receptors and the intrinsic pathway via DNA damage and reactive oxygen species (ROS) formation. In this study we investigated the effect of catalase and CuZn-superoxide ... More
Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1.
AuthorsLu H, Dalgard CL, Mohyeldin A, McFate T, Tait AS, Verma A
JournalJ Biol Chem
PubMed ID16223732
Continuous hydroxylation of the HIF-1 transcription factor alpha subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1alpha hydroxylation and thus activates HIF-1alpha-mediated gene expression. Several nonhypoxic ... More
Respiratory chain components involved in the glycerophosphate dehydrogenase-dependent ROS production by brown adipose tissue mitochondria.
AuthorsVrbacký M, Drahota Z, Mrácek T, Vojtísková A, Jesina P, Stopka P, Houstek J
JournalBiochim Biophys Acta
PubMed ID17560536
Involvement of mammalian mitochondrial glycerophosphate dehydrogenase (mGPDH, EC 1.1.99.5) in reactive oxygen species (ROS) generation was studied in brown adipose tissue mitochondria by different spectroscopic techniques. Spectrofluorometry using ROS-sensitive probes CM-H2DCFDA and Amplex Red was used to determine the glycerophosphate- or succinate-dependent ROS production in mitochondria supplemented with respiratory chain ... More
Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade.
AuthorsMahadev K, Zilbering A, Zhu L, Goldstein BJ
JournalJ Biol Chem
PubMed ID11297536
The insulin signaling pathway is activated by tyrosine phosphorylation of the insulin receptor and key post-receptor substrate proteins and balanced by the action of specific protein-tyrosine phosphatases (PTPases). PTPase activity, in turn, is highly regulated in vivo by oxidation/reduction reactions involving the cysteine thiol moiety required for catalysis. Here we ... More
Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress.
Mitochondria can be a source of reactive oxygen species (ROS) and a target of oxidative damage during oxidative stress. In this connection, the effect of photodynamic treatment (PDT) with Mitotracker Red (MR) as a mitochondria-targeted photosensitizer has been studied in HeLa cells. It is shown that MR produces both singlet ... More
Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas.
We describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy. Two bispecific HexAbs [IgG-(Fab)(4) constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, ... More
The HIV-1 Nef protein and phagocyte NADPH oxidase activation.
AuthorsVilhardt F, Plastre O, Sawada M, Suzuki K, Wiznerowicz M, Kiyokawa E, Trono D, Krause KH
JournalJ Biol Chem
PubMed ID12207012
Nef, a multifunctional HIV protein, activates the Vav/Rac/p21-activated kinase (PAK) signaling pathway. Given the potential role of this pathway in the activation of the phagocyte NADPH oxidase, we have investigated the effect of the HIV-1 Nef protein on the phagocyte respiratory burst. Microglia (cell line and primary culture) were transduced ... More
Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes.
AuthorsAon MA, Cortassa S, Marbán E, O'Rourke B
JournalJ Biol Chem
PubMed ID12930841
Reactive oxygen species (ROS) and/or Ca2+ overload can trigger depolarization of mitochondrial inner membrane potential (DeltaPsim) and cell injury. Little is known about how loss of DeltaPsim in a small number of mitochondria might influence the overall function of the cell. Here we employ the narrow focal excitation volume of ... More
Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells.
AuthorsMizukami Y, Jo WS, Duerr EM, Gala M, Li J, Zhang X, Zimmer MA, Iliopoulos O, Zukerberg LR, Kohgo Y, Lynch MP, Rueda BR, Chung DC
JournalNat Med
PubMed ID16127434
Hypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis. It represents an attractive therapeutic target in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy. But it is unclear ... More
Inositol 1,4,5-trisphosphate-induced Ca2+ release is inhibited by mitochondrial depolarization.
AuthorsCollins TJ, Lipp P, Berridge MJ, Li W, Bootman MD
JournalBiochem J
PubMed ID10749691
We investigated the consequences of depolarizing the mitochondrial membrane potential (Deltapsi(mit)) on Ca(2+) signals arising via inositol 1,4,5-trisphosphate receptors (InsP(3)R) in hormone-stimulated HeLa cells. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or a mixture of antimycin A+oligomycin were found to rapidly depolarize Deltapsi(mit). Mitochondrial depolarization enhanced the number of cells responding to a ... More
Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production.
AuthorsYe G, Metreveli NS, Ren J, Epstein PN
JournalDiabetes
PubMed ID12606520
Many individuals with diabetes experience impaired cardiac contractility that cannot be explained by hypertension and atherosclerosis. This cardiomyopathy may be due to either organ-based damage, such as fibrosis, or to direct damage to cardiomyocytes. Reactive oxygen species (ROS) have been proposed to contribute to such damage. To address these hypotheses, ... More
Oxidant-injured airway epithelial cells upregulate thioredoxin but do not produce interleukin-8.
We tested the hypothesis that oxidant-injured cells upregulate thioredoxin, whereas oxidant-stressed, but not injured, cells upregulate interleukin (IL)-8 after injury. We exposed primary human tracheobronchial epithelial cells and transformed human bronchial epithelial cells (BEAS-2B S.6) to 0, 200, 400, or 600 microM H(2)O(2) for 1 h followed by an additional ... More
Potentiation of chlorin e6 photodynamic activity in vitro with peptide-based intracellular vehicles.
AuthorsBisland SK, Singh D, Gariépy J
JournalBioconjug Chem
PubMed ID10563767
Photodynamic therapy (PDT) is a targeted treatment modality where photosensitizers accumulate into cells and are selectively activated by light leading to the production of toxic species and cell death. Focusing the action of photosensitizers to a unique intracellular target may enhance their cytotoxicity. In this study, we demonstrate that the ... More
Distinct domains for anti- and pro-apoptotic activities of IEX-1.
AuthorsShen L, Guo J, Santos-Berrios C, Wu MX
JournalJ Biol Chem
PubMed ID16567805
IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its overexpression can suppress or enhance apoptosis dependent on the nature of stress, yet the polypeptide does not possess any of the functional domains that are homologous to those present in well characterized effectors or inhibitors of apoptosis. This study ... More
Menadione-induced reactive oxygen species generation via redox cycling promotes apoptosis of murine pancreatic acinar cells.
Oxidative stress may be an important determinant of the severity of acute pancreatitis. One-electron reduction of oxidants generates reactive oxygen species (ROS) via redox cycling, whereas two-electron detoxification, e.g. by NAD(P)H:quinone oxidoreductase, does not. The actions of menadione on ROS production and cell fate were compared with those of a ... More
Sequential opening of mitochondrial ion channels as a function of glutathione redox thiol status.
AuthorsAon MA, Cortassa S, Maack C, O'Rourke B
JournalJ Biol Chem
PubMed ID17540766
Mitochondrial membrane potential (DeltaPsi(m)) depolarization contributes to cell death and electrical and contractile dysfunction in the post-ischemic heart. An imbalance between mitochondrial reactive oxygen species production and scavenging was previously implicated in the activation of an inner membrane anion channel (IMAC), distinct from the permeability transition pore (PTP), as the ... More
Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity.
AuthorsLe SB, Hailer MK, Buhrow S, Wang Q, Flatten K, Pediaditakis P, Bible KC, Lewis LD, Sausville EA, Pang YP, Ames MM, Lemasters JJ, Holmuhamedov EL, Kaufmann SH
JournalJ Biol Chem
PubMed ID17213201
Adaphostin is a dihydroquinone derivative that is undergoing extensive preclinical testing as a potential anticancer drug. Previous studies have suggested that the generation of reactive oxygen species (ROS) plays a critical role in the cytotoxicity of this agent. In this study, we investigated the source of these ROS. Consistent with ... More
Endosomal acidification and activation of NADPH oxidase isoforms are upstream events in hyperosmolarity-induced hepatocyte apoptosis.
AuthorsReinehr R, Becker S, Braun J, Eberle A, Grether-Beck S, Haüssinger D
JournalJ Biol Chem
PubMed ID16772302
Hyperosmotic exposure of rat hepatocytes induced a rapid oxidative-stress(ROS) response as an upstream signal for proapoptotic CD95 activation. This study shows that hyperosmotic ROS formation involves a rapid ceramide- and protein kinase Czeta (PKCzeta)-dependent serine phosphorylation of p47phox and subsequent activation of NADPH oxidase isoforms. Hyperosmotic p47phox phosphorylation and ROS ... More
The role of polyamine catabolism in polyamine analogue-induced programmed cell death.
AuthorsHa HC, Woster PM, Yager JD, Casero RA
JournalProc Natl Acad Sci U S A
PubMed ID9326648
N1-ethyl-N11-[(cyclopropyl)methyl]-4,8,-diazaundecane (CPENSpm) is a polyamine analogue that represents a new class of antitumor agents that demonstrate phenotype-specific cytotoxic activity. However, the precise mechanism of its selective cytotoxic activity is not known. CPENSpm treatment results in the superinduction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) in sensitive cell types and ... More
Overstimulation of PrPC signaling pathways by prion peptide 106-126 causes oxidative injury of bioaminergic neuronal cells.
AuthorsPietri M, Caprini A, Mouillet-Richard S, Pradines E, Ermonval M, Grassi J, Kellermann O, Schneider B
JournalJ Biol Chem
PubMed ID16864581
Transmissible spongiform encephalopathies, also called prion diseases, are characterized by neuronal loss linked to the accumulation of PrP(Sc), a pathologic variant of the cellular prion protein (PrP(C)). Although the molecular and cellular bases of PrP(Sc)-induced neuropathogenesis are not yet fully understood, increasing evidence supports the view that PrP(Sc) accumulation interferes ... More
Mutagenicity of cadmium in mammalian cells: implication of oxidative DNA damage.
AuthorsFilipic M, Hei TK
JournalMutat Res
PubMed ID14757196
Cadmium and cadmium compounds are well established human carcinogens and are ubiquitously present in the environment. The carcinogenic mechanism(s) of cadmium remains largely unknown since direct mutagenic effect is weak in bacterial and in standard mammalian cell mutation assays. In this study, we show that when evaluated using the human-hamster ... More
Dual role of peroxiredoxin I in macrophage-derived foam cells.
AuthorsConway JP, Kinter M
JournalJ Biol Chem
PubMed ID16880205
We and others have shown that foam cell formation initiated by exposing macrophages to oxidized low density lipoprotein (oxLDL) triggers the differential expression of a number of proteins. Specifically, our experiments have identified peroxiredoxin I (Prx I) as one of these up-regulated proteins. The peroxiredoxins, a family of peroxidases initially ... More
2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) directly targets mitochondrial glutathione to induce apoptosis in pancreatic cancer.
AuthorsSamudio I, Konopleva M, Hail N, Shi YX, McQueen T, Hsu T, Evans R, Honda T, Gribble GW, Sporn M, Gilbert HF, Safe S, Andreeff M
JournalJ Biol Chem
PubMed ID16118208
Surgical resection is the only curative strategy for pancreatic cancer (PC). Unfortunately, >80% of pancreatic cancer patients bear inoperable, locally advanced, chemoresistant tumors demonstrating the urgent need for development of novel therapeutic approaches to treat this disease. Here we report that the synthetic triterpenoid 2-cyano-3,12 dioxooleana-1,9 dien-28-imidazolide (CDDO-Im) antagonizes PC ... More
Autophagy contributes to caspase-independent macrophage cell death.
AuthorsXu Y, Kim SO, Li Y, Han J
JournalJ Biol Chem
PubMed ID16702227
Macrophage cell death plays a role in many physiological and pathophysiological conditions. Previous work has shown that macrophages can undergo caspase-independent cell death, and this process is associated with Nur77 induction, which is involved in inducing chromatin condensation and DNA fragmentation. Here we show that autophagy is a cytosolic event ... More
Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney.
AuthorsDoi K, Suzuki Y, Nakao A, Fujita T, Noiri E
JournalKidney Int
PubMed ID15086910
BACKGROUND: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of free radicals and has the antioxidant ability to inhibit lipid peroxidation. Its protective effect on brain ischemia has been shown. This study aimed to elucidate its possible therapeutic effects on renal oxidative stress in a rat ischemia/reperfusion model. METHODS: Ischemic acute renal ... More
Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats.
AuthorsObrosova IG, Minchenko AG, Vasupuram R, White L, Abatan OI, Kumagai AK, Frank RN, Stevens MJ
JournalDiabetes
PubMed ID12606532
The study addressed the role for aldose reductase (AR) in 1) retinal oxidative stress and vascular endothelial growth factor (VEGF) overexpression in early diabetes, and 2) high glucose-induced oxidative stress in retinal endothelial cells. In vivo experiments were performed on control rats and diabetic rats treated with or without low ... More
The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species.
AuthorsLin Y, Berg AH, Iyengar P, Lam TK, Giacca A, Combs TP, Rajala MW, Du X, Rollman B, Li W, Hawkins M, Barzilai N, Rhodes CJ, Fantus IG, Brownlee M, Scherer PE
JournalJ Biol Chem
PubMed ID15536073
Hyperglycemia is a major independent risk factor for diabetic macrovascular disease. The consequences of exposure of endothelial cells to hyperglycemia are well established. However, little is known about how adipocytes respond to both acute as well as chronic exposure to physiological levels of hyperglycemia. Here, we analyze adipocytes exposed to ... More
Simultaneous intracellular calcium and sodium flux imaging in human vanilloid receptor 1 (VR1)-transfected human embryonic kidney cells: a method to resolve ionic dependence of VR1-mediated cell death.
AuthorsGrant ER, Dubin AE, Zhang SP, Zivin RA, Zhong Z
JournalJ Pharmacol Exp Ther
PubMed ID11752091
The vanilloid receptor 1 (VR1) is a ligand-gated, nonselective cation channel important for the sensory processing of painful stimuli. Activation of VR1 leads to increases in intracellular concentrations of calcium and sodium. Prolonged activation of VR1 in mammalian expression systems leads to cell death. The mechanism of VR1-mediated toxicity may ... More
Intracellular reactive oxygen species mediate the linkage of Na+/K+-ATPase to hypertrophy and its marker genes in cardiac myocytes.
AuthorsXie Z, Kometiani P, Liu J, Li J, Shapiro JI, Askari A
JournalJ Biol Chem
PubMed ID10383443
We showed before that in cardiac myocytes partial inhibition of Na+/K+-ATPase by nontoxic concentrations of ouabain causes hypertrophy and transcriptional regulations of growth-related marker genes through multiple Ca2+-dependent signal pathways many of which involve Ras and p42/44 mitogen-activated protein kinases. The aim of this work was to explore the roles ... More