Superoxide dismutase mimetics: synthesis and structure-activity relationship study of MnTBAP analogues.
AuthorsGauuan PJ, Trova MP, Gregor-Boros L, Bocckino SB, Crapo JD, Day BJ
JournalBioorg Med Chem
PubMed ID12110324
Carboxylic ester and amide-substituted analogues of [5,10,15,20-tetrakis(4-carboxyphenyl)-porphyrinato]manganese(III) chloride (MnTBAP) were synthesized and assayed as potential superoxide dismutase (SOD) mimetics. The tetraester analogues 4a and 4b were found to have comparable SOD activity to the known SOD mimetic MnTBAP, while amides 4c-4e exhibited reduced SOD activity. In the substituted methyl benzoate/acid ... More
Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission.
AuthorsDagda RK, Cherra SJ, Kulich SM, Tandon A, Park D, Chu CT,
JournalJ Biol Chem
PubMed ID19279012
'Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy ... More
Imaging and analysis of 3D tumor spheroids enriched for a cancer stem cell phenotype.
AuthorsRobertson FM, Ogasawara MA, Ye Z, Chu K, Pickei R, Debeb BG, Woodward WA, Hittelman WN, Cristofanilli M, Barsky SH,
JournalJ Biomol Screen
PubMed ID20639504
'Tumors that display a highly metastatic phenotype contain subpopulations of cells that display characteristics similar to embryonic stem cells. These cells exhibit the ability to undergo self-renewal; slowly replicate to retain a nucleoside analog label, leading to their definition as ' ... More
Subcellular localization of Nox4 and regulation in diabetes.
AuthorsBlock K, Gorin Y, Abboud HE,
JournalProc Natl Acad Sci U S A
PubMed ID19706525
'Oxidative stress is implicated in human diseases. Some of the oxidative pathways are harbored in the mitochondria. NAD(P)H oxidases have been identified not only in phagocytic but also in somatic cells. Nox4 is the most ubiquitous of these oxidases and is a major source of reactive oxygen species (ROS) in ... More
'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress.
AuthorsJohnson-Cadwell LI, Jekabsons MB, Wang A, Polster BM, Nicholls DG
JournalJ Neurochem
PubMed ID17437552
'Cultured rat cerebellar granule neurons were incubated with low nanomolar concentrations of the protonophore carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) to test the hypothesis that ''mild uncoupling'' could be neuroprotective by decreasing oxidative stress. To quantify the uncoupling, respiration and mitochondrial membrane potential (Deltapsi(m)) were determined in parallel as a function of FCCP ... More
Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels.
Authorsde Bilbao F, Arsenijevic D, Vallet P, Hjelle OP, Ottersen OP, Bouras C, Raffin Y, Abou K, Langhans W, Collins S, Plamondon J, Alves-Guerra MC, Haguenauer A, Garcia I, Richard D, Ricquier D, Giannakopoulos P
JournalJ Neurochem
PubMed ID15147521
'Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen species production in mitochondria. We performed a detailed study of brain injury, including regional and cellular distribution of UCP2 mRNA, as well as measures of oxidative stress markers following permanent middle cerebral artery occlusion in UCP2 knockout ... More
Mapping mechanisms and charting the time course of premature cell senescence and apoptosis: lysosomal dysfunction and ganglioside accumulation in endothelial cells.
AuthorsPatschan S, Chen J, Gealekman O, Krupincza K, Wang M, Shu L, Shayman JA, Goligorsky MS,
JournalAm J Physiol Renal Physiol
PubMed ID17928415
'Endothelial cells subjected to glycated collagen I develop premature senescence within 3-5 days, as revealed by increased senescence-associated beta-galactosidase activity, decreased proliferation, and an increase in cell size. Here, we analyzed the time course and possible mechanisms of this process. Lysosomal integrity studies revealed a rapid collapse of pH gradient ... More
Elevated mitochondrial reactive oxygen species generation affects the immune response via hypoxia-inducible factor-1alpha in long-lived Mclk1+/- mouse mutants.
AuthorsWang D, Malo D, Hekimi S,
JournalJ Immunol
PubMed ID20007531
'Mitochondrial reactive oxygen species (ROS) are believed to stabilize hypoxia-inducible factor (HIF)-1alpha, a transcriptional regulator of the immune response. Mclk1 encodes a mitochondrial protein that is necessary for ubiquinone biosynthesis. Heterozygote Mclk1(+/-) mutant mice are long-lived despite increased mitochondrial ROS and decreased energy metabolism. In this study, Mclk1(+/-) mutant mice ... More
A role for mitochondria in NLRP3 inflammasome activation.
AuthorsZhou R, Yazdi AS, Menu P, Tschopp J,
JournalNature
PubMed ID21124315
'An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host ''danger'', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we ... More
Mitochondrial depolarization following hydrogen sulfide exposure in erythrocytes from a sulfide-tolerant marine invertebrate.
AuthorsJulian D, April KL, Patel S, Stein JR, Wohlgemuth SE
JournalJ Exp Biol
PubMed ID16244170
'Sulfide-tolerant marine invertebrates employ a variety of mechanisms to detoxify sulfide once it has entered their bodies, but their integumentary, respiratory epithelium and circulatory cells may still be exposed to toxic sulfide concentrations. To investigate whether sulfide exposure is toxic to mitochondria of a sulfide-tolerant invertebrate, we used the fluorescent ... More
Nullomer derived anticancer peptides (NulloPs): differential lethal effects on normal and cancer cells in vitro.
AuthorsAlileche A, Goswami J, Bourland W, Davis M, Hampikian G,
JournalPeptides
PubMed ID23000474
'We demonstrate the first use of the nullomer (absent sequences) approach to drug discovery and development. Nullomers are the shortest absent sequences determined in a species, or group of species. By identifying the shortest absent peptide sequences from the NCBI databases, we screened several potential anti-cancer peptides. In order to ... More
Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1.
AuthorsOoe H, Taira T, Iguchi-Ariga SM, Ariga H
JournalToxicol Sci
PubMed ID16093527
'DJ-1 was first identified as an activated ras-dependent oncogene. DJ-1 is related to male fertility, and its expression in sperm decreases in response to exposure to a number of reproductive toxicants. DJ-1 has been associated with the onset of familial Parkinson''s disease (PD) in humans, and has been found to ... More
Selective fluorescent imaging of superoxide in vivo using ethidium-based probes.
AuthorsRobinson KM, Janes MS, Pehar M, Monette JS, Ross MF, Hagen TM, Murphy MP, Beckman JS
JournalProc Natl Acad Sci U S A
PubMed ID17015830
'The putative oxidation of hydroethidine (HE) has become a widely used fluorescent assay for the detection of superoxide in cultured cells. By covalently joining HE to a hexyl triphenylphosphonium cation (Mito-HE), the HE moiety can be targeted to mitochondria. However, the specificity of HE and Mito-HE for superoxide in vivo ... More
Mutant SOD1-induced neuronal toxicity is mediated by increased mitochondrial superoxide levels.
AuthorsZimmerman MC, Oberley LW, Flanagan SW
JournalJ Neurochem
PubMed ID17394531
'Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease in adults, is characterized by the selective degeneration and death of motor neurons leading to progressive paralysis and eventually death. Approximately 20% of familial ALS cases are associated with mutations in SOD1, the gene encoding Cu/Zn-superoxide dismutase (CuZnSOD). Previously, we ... More
SOD2 contributes to anti-oxidative capacity in rabbit corneal endothelial cells.
AuthorsLiu C, Ogando D, Bonanno JA,
JournalMol Vis
PubMed ID21976958
'Corneal endothelial cells are rich in mitochondria, a potential source of reactive oxygen species (ROS). ROS have been implicated in endothelial cell loss during aging or in endothelial dystrophies. In this study we examined the anti-oxidative role of mitochondrial superoxide dismutase (SOD2) in corneal endothelial cells. SOD2 expression was examined ... 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
Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy.
AuthorsMukhopadhyay P, Rajesh M, Haskó G, Hawkins BJ, Madesh M, Pacher P
JournalNat Protoc
PubMed ID17853886
'Annexin V and Sytox Green are widely used markers to evaluate apoptosis in various cell types using flow cytometry and fluorescent microscopy. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated for confocal microscopy and flow cytometry. ... More
Resolution of mitochondrial oxidative stress rescues coronary collateral growth in Zucker obese fatty rats.
'We have previously found abrogated ischemia-induced coronary collateral growth in Zucker obese fatty (ZOF) rats compared with Zucker lean (ZLN) rats. Because ZOF rats have structural abnormalities in their mitochondria suggesting dysfunction and also show increased production of O(2), we hypothesized that mitochondrial dysfunction caused by oxidative stress impairs coronary ... More
Amyloid ß-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide.
AuthorsMa T, Hoeffer CA, Wong H, Massaad CA, Zhou P, Iadecola C, Murphy MP, Pautler RG, Klann E,
JournalJ Neurosci
PubMed ID21490199
'Generation of reactive oxygen species (ROS) causes cellular oxidative damage and has been implicated in the etiology of Alzheimer''s disease (AD). In contrast, multiple lines of evidence indicate that ROS can normally modulate long-term potentiation (LTP), a cellular model for memory formation. We recently showed that decreasing the level of ... More
Sensory neurons and schwann cells respond to oxidative stress by increasing antioxidant defense mechanisms.
AuthorsVincent AM, Kato K, McLean LL, Soules ME, Feldman EL,
JournalAntioxid Redox Signal
PubMed ID19072199
'Elevated blood glucose is a key initiator of mechanisms leading to diabetic neuropathy. Increases in glucose induce acute mitochondrial oxidative stress in dorsal root ganglion (DRG) neurons, the sensory neurons normally affected in diabetic neuropathy, whereas Schwann cells are largely unaffected. We propose that activation of an antioxidant response in ... 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
Phosphoaspirin (MDC-43), a novel benzyl ester of aspirin, inhibits the growth of human cancer cell lines more potently than aspirin: a redox-dependent effect.
'Aspirin is chemopreventive against colon and probably other cancers, but this effect is relatively weak and its chronic administration to humans is associated with significant side effects. Because of these limitations, extensive effort has been exerted to improve the pharmacological properties of aspirin. We have determined the anticancer activity and ... More
Simple quantitative detection of mitochondrial superoxide production in live cells.
AuthorsMukhopadhyay P, Rajesh M, Yoshihiro K, Haskó G, Pacher P
JournalBiochem Biophys Res Commun
PubMed ID17475217
'Experiments with isolated mitochondria have established that these organelles are pivotal intracellular sources of superoxide in a variety of pathophysiological conditions. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated with confocal microscopy. Here we show approximately ... More
?-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor.
'Reactive oxygen species regulate redox-signaling processes, but in excess they can cause cell damage, hence underlying the aetiology of several neurological diseases. Through its ability to down modulate reactive oxygen species, glutathione is considered an essential thiol-antioxidant derivative, yet under certain circumstances it is dispensable for cell growth and redox ... 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
Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro.
AuthorsMukhopadhyay P, Rajesh M, Bátkai S, Kashiwaya Y, Haskó G, Liaudet L, Szabó C, Pacher P,
JournalAm J Physiol Heart Circ Physiol
PubMed ID19286953
'Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mechanisms are elusive. Here, we explore the role of superoxide, nitric oxide (NO), and peroxynitrite in DOX-induced cell death using both ... More
Trypanosoma cruzi induces the reactive oxygen species-PARP-1-RelA pathway for up-regulation of cytokine expression in cardiomyocytes.
AuthorsBa X, Gupta S, Davidson M, Garg NJ,
JournalJ Biol Chem
PubMed ID20145242
'In this study, we demonstrate that human cardiomyocytes (AC16) produce reactive oxygen species (ROS) and inflammatory cytokines in response to Trypanosoma cruzi. ROS were primarily produced by mitochondria, some of which diffused to cytosol of infected cardiomyocytes. These ROS resulted in an increase in 8-hydroxyguanine lesions and DNA fragmentation that ... 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
Detection of 2-hydroxyethidium in cellular systems: a unique marker product of superoxide and hydroethidine.
'Various detection methods of the specific product of reaction of superoxide (O(2)(*-)) with hydroethidine (HE), namely 2-hydroxyethidium (2-OH-E(+)), and with its mitochondria-targeted analog are described. The detailed protocol for quantification of 2-OH-E(+), the unique product of HE/O(2)(*-) in cellular systems, is presented. The procedure includes cell lysis, protein precipitation using ... More
Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa.
'CONTEXT: Male infertility has been linked with the excessive generation of reactive oxygen species (ROS) by defective spermatozoa. However, the subcellular origins of this activity are unclear. OBJECTIVE: The objective of this study was to determine the importance of sperm mitochondria in creating the oxidative stress associated with defective sperm ... More
Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.
AuthorsRajesh M, Mukhopadhyay P, Bátkai S, Haskó G, Liaudet L, Drel VR, Obrosova IG, Pacher P
JournalAm J Physiol Heart Circ Physiol
PubMed ID17384130
'A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on ... More
Heat stress leads to superoxide formation in Bacillus cereus detected using the fluorescent probe MitoSOX.
AuthorsMols M, Ceragioli M, Abee T,
JournalInt J Food Microbiol
PubMed ID21872960
'Bacillus cereus is a food-borne human pathogen and food spoilage organism. Spores and vegetative cells of B. cereus can be found almost everywhere and therefore often end up in food processing equipment and food products. To remove spores and vegetative cells from food or equipment, harsh treatments such as high ... More
Chapter 24 Quantification, localization, and tissue specificities of mouse mitochondrial reactive oxygen species production.
Mitochondria play a critical role in many different pathologic conditions. Increasing evidence has shown that mitochondrial reactive oxygen species (ROS) production may provide an etiologic link between mitochondria and pathologics. The widespread use of laboratory mice as models for a host of human diseases makes the quantification and localization of ... More
cAMP controls oxygen metabolism in mammalian cells.
AuthorsPiccoli C, Scacco S, Bellomo F, Signorile A, Iuso A, Boffoli D, Scrima R, Capitanio N, Papa S
JournalFEBS Lett
PubMed ID16870178
The impact of cAMP on ROS-balance in human and mammalian cell cultures was studied. cAMP reduced accumulation of ROS induced by serum-limitation, under conditions in which there was no significant change in the activity of scavenger systems. This effect was associated with cAMP-dependent activation of the NADH-ubiquinone oxidoreductase activity of ... More
Superoxide dismutase and the death of motoneurons in ALS.
AuthorsBeckman JS, Estévez AG, Crow JP, Barbeito L
JournalTrends Neurosci
PubMed ID11881740
Amyotrophic lateral sclerosis (ALS) is a lethal disease that is characterized by the relentless death of motoneurons. Mutations to Cu-Zn superoxide dismutase (SOD), though occurring in just 2-3% of individuals with ALS, remain the only proven cause of the disease. These mutations structurally weaken SOD, which indirectly decreases its affinity ... More
The selective detection of mitochondrial superoxide by live cell imaging.
AuthorsRobinson KM, Janes MS, Beckman JS,
JournalNat Protoc
PubMed ID18536642
A general protocol is described to improve the specificity for imaging superoxide formation in live cells via fluorescence microscopy with either hydroethidine (HE) or its mitochondrially targeted derivative Mito-HE (MitoSOX Red). Two different excitation wavelengths are used to distinguish the superoxide-dependent hydroxylation of Mito-HE (385-405 nm) from the nonspecific formation ... More
Acyl-CoA-induced generation of reactive oxygen species in mitochondrial preparations is due to the presence of peroxisomes.
AuthorsSchönfeld P, Dymkowska D, Wojtczak L,
JournalFree Radic Biol Med
PubMed ID19442717
Preparations of rat liver mitochondria, but not of brain and heart mitochondria, produce large quantities of reactive oxygen species (ROS) in the presence of palmitoyl-CoA and other long-chain acyl-CoAs. Palmitoyl-CoA inhibited respiration of rat liver mitochondria with glutamate plus malate or with succinate as substrate. However, ROS production induced by ... More
Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities.
AuthorsOng MM, Latchoumycandane C, Boelsterli UA,
JournalToxicol Sci
PubMed ID17150972
Troglitazone, a first-generation thiazolidinedione antidiabetic drug, was withdrawn from the market due to an unacceptable risk of idiosyncratic hepatotoxicity. Troglitazone does not cause hepatotoxicity in normal healthy rodents, but it produces mitochondrial injury in vitro at high concentrations. The aim of this study was to explore whether genetic mitochondrial abnormalities ... More
Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation.
AuthorsLee SJ, Ryter SW, Xu JF, Nakahira K, Kim HP, Choi AM, Kim YS,
JournalAm J Respir Cell Mol Biol
PubMed ID21441382
Autophagy, an autodigestive process that degrades cellular organelles and protein, plays an important role in maintaining cellular homeostasis during environmental stress. Carbon monoxide (CO), a toxic gas and candidate therapeutic molecule, confers cytoprotection in animal models of acute lung injury. The mechanisms underlying CO-dependent lung cell protection and the role ... More
Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production.
AuthorsTang S, Le PK, Tse S, Wallace DC, Huang T,
JournalPLoS One
PubMed ID19221591
Optic atrophy 1 (OPA1) is a dynamin-like GTPase located in the inner mitochondrial membrane and mutations in OPA1 are associated with autosomal dominant optic atrophy (DOA). OPA1 plays important roles in mitochondrial fusion, cristae remodeling and apoptosis. Our previous study showed that dOpa1 mutation caused elevated reactive oxygen species (ROS) ... More
Oxidative stress induces degradation of mitochondrial DNA.
AuthorsShokolenko I, Venediktova N, Bochkareva A, Wilson GL, Alexeyev MF,
JournalNucleic Acids Res
PubMed ID19264794
Mitochondrial DNA (mtDNA) is located in close proximity of the respiratory chains, which are the main cellular source of reactive oxygen species (ROS). ROS can induce oxidative base lesions in mtDNA and are believed to be an important cause of the mtDNA mutations, which accumulate with aging and in diseased ... More
Proline accumulation is inhibitory to Arabidopsis seedlings during heat stress.
AuthorsLv WT, Lin B, Zhang M, Hua XJ,
JournalPlant Physiol
PubMed ID21670222
The effect of proline (Pro) accumulation on heat sensitivity was investigated using transgenic Arabidopsis (Arabidopsis thaliana) plants ectopically expressing the ?(1)-pyrroline-5-carboxylate synthetase 1 gene (AtP5CS1) under the control of a heat shock protein 17.6II gene promoter. During heat stress, the heat-inducible expression of the AtP5CS1 transgene was capable of enhancing ... More
Role of Bim in diallyl trisulfide-induced cytotoxicity in human cancer cells.
AuthorsLee BC, Park BH, Kim SY, Lee YJ,
JournalJ Cell Biochem
PubMed ID21053278
The aim of this study was to investigate the effect of garlic constituent diallyl trisulfide (DATS) on the cell-death signaling pathway in a human breast cell line (MDA-MB-231). We observed that DATS (10-100?µM) treatment resulted in dose- and time-dependent cytotoxicity. Treatment of MDA-MB-231 cells with a cytotoxicity inducing concentration of ... More
Impaired balance of mitochondrial fission and fusion in Alzheimer's disease.
AuthorsWang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X,
JournalJ Neurosci
PubMed ID19605646
Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) neurons. In this study, we explored the involvement of an abnormal mitochondrial dynamics by investigating the changes in the expression of mitochondrial fission and fusion proteins in AD brain and the potential cause and consequence of these changes in neuronal ... More
Mitochondria-derived reactive oxygen species mediate heme oxygenase-1 expression in sheared endothelial cells.
Bovine aortic endothelial cells (ECs) respond to nitric oxide (NO) donors by activating the redox-sensitive NF-E2-related factor 2/antioxidant response element pathway and up-regulating heme oxygenase (HO)-1 expression. EC exposure to steady laminar shear stress causes a sustained increase in NO, a transient increase in reactive oxygen species (ROS), and activation ... More
Identification of a protective role for protein phosphatase 1cgamma1 against oxidative stress-induced vascular smooth muscle cell apoptosis.
AuthorsTchivilev I, Madamanchi NR, Vendrov AE, Niu XL, Runge MS,
JournalJ Biol Chem
PubMed ID18540044
The development of therapeutic strategies to inhibit reactive oxygen species (ROS)-mediated damage in blood vessels has been limited by a lack of specific targets for intervention. Targeting ROS-mediated events in the vessel wall is of interest, because ROS play important roles throughout atherogenesis. In early atherosclerosis, ROS stimulate vascular smooth ... More
AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects.
AuthorsDavies NJ, Hayden RE, Simpson PJ, Birtwistle J, Mayer K, Ride JP, Bunce CM,
JournalCancer Res
PubMed ID19487289
Members of the aldo-keto reductase (AKR) superfamily, particularly the AKR1C subfamily, are emerging as important mediators of the pathology of cancer. Agents that inhibit these enzymes may provide novel agents for either the chemoprevention or treatment of diverse malignancies. Recently, jasmonates, a family of plant stress hormones that bear a ... More
Chelation of lysosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells from hydrogen peroxide toxicity by precluding autophagy and Akt dephosphorylation.
AuthorsCastino R, Fiorentino I, Cagnin M, Giovia A, Isidoro C,
JournalToxicol Sci
PubMed ID21742779
In human neuroblastoma SH-SY5Y cells, hydrogen peroxide (H(2)O(2), 200µM) rapidly (< 5 min) induced autophagy, as shown by processing and vacuolar relocation of light chain 3(LC3). Accumulation of autophagosome peaked at 30 min of H(2)O(2) exposure. The continuous presence of H(2)O(2) eventually (at > 60 min) caused autophagy-dependent annexin V-positive ... More
A water soluble CoQ10 formulation improves intracellular distribution and promotes mitochondrial respiration in cultured cells.
AuthorsBergamini C, Moruzzi N, Sblendido A, Lenaz G, Fato R,
JournalPLoS One
PubMed ID22432044
Mitochondria are both the cellular powerhouse and the major source of reactive oxygen species. Coenzyme Q(10) plays a key role in mitochondrial energy production and is recognized as a powerful antioxidant. For these reasons it can be argued that higher mitochondrial ubiquinone levels may enhance the energy state and protect ... More
Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress response in HeLa cells.
AuthorsHosoki A, Yonekura S, Zhao QL, Wei ZL, Takasaki I, Tabuchi Y, Wang LL, Hasuike S, Nomura T, Tachibana A, Hashiguchi K, Yonei S, Kondo T, Zhang-Akiyama QM,
JournalJ Radiat Res
PubMed ID22302046
Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx ... More
Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone.
AuthorsYadava N, Nicholls DG,
JournalJ Neurosci
PubMed ID17611283
Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 ... More
Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in TriPeptidyl Peptidase-1 (TPP-1) deficient fibroblasts.
AuthorsVan Beersel G, Tihon E, Demine S, Hamer I, Jadot M, Arnould T,
JournalBiosci Rep
PubMed ID23249249
The Neuronal Ceroid Lipofuscinosis (NCLs) form a group of 8 inherited autosomal recessive diseases characterized by the intralysosomal accumulation of autofluorescent pigments, called ceroids. Recent data suggest that the pathogenesis of NCLs is associated with the appearance of fragmented mitochondria with altered functions. However, even if an impairement in the ... More
MAO-B elevation in mouse brain astrocytes results in Parkinson's pathology.
AuthorsMallajosyula JK, Kaur D, Chinta SJ, Rajagopalan S, Rane A, Nicholls DG, Di Monte DA, Macarthur H, Andersen JK,
JournalPLoS ONE
PubMed ID18286173
Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were ... More
Prolonged production of reactive oxygen species in response to B cell receptor stimulation promotes B cell activation and proliferation.
AuthorsWheeler ML, Defranco AL,
JournalJ Immunol
PubMed ID23024271
We have investigated the intracellular sources and physiological function of reactive oxygen species (ROS) produced in primary B cells in response to BCR stimulation. BCR stimulation of primary resting murine B cells induced the rapid production of ROS that occurred within minutes and was maintained for at least 24 h ... More
Regulation by mitochondrial superoxide and NADPH oxidase of cellular formation of nitrated cyclic GMP: potential implications for ROS signalling.
AuthorsAhmed KA, Sawa T, Ihara H, Kasamatsu S, Yoshitake J, Rahaman MM, Okamoto T, Fujii S, Akaike T,
JournalBiochem J
PubMed ID21967515
8-Nitro-cGMP (8-nitroguanosine 3',5'-cyclic monophosphate) is a nitrated derivative of cGMP, which can function as a unique electrophilic second messenger involved in regulation of an antioxidant adaptive response in cells. In the present study, we investigated chemical and biochemical regulatory mechanisms involved in 8-nitro-cGMP formation, with particular focus on the roles ... More
Mechanism of cell death caused by complex I defects in a rat dopaminergic cell line.
AuthorsMarella M, Seo BB, Matsuno-Yagi A, Yagi T,
JournalJ Biol Chem
PubMed ID17581813
Defects in the proton-translocating NADH-quinone oxidoreductase (complex I) of mammalian mitochondria are linked to neurodegenerative disorders. The mechanism leading to cell death elicited by complex I deficiency remains elusive. We have shown that expression of a rotenone-insensitive yeast NADH-quinone oxidoreductase (Ndi1) can rescue mammalian cells from complex I dysfunction. By ... More
Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.
AuthorsBrown CO, Salem K, Wagner BA, Bera S, Singh N, Tiwari A, Choudhury A, Buettner GR, Goel A,
JournalBiochem J
PubMed ID22471522
IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative ... More
Nrf2 signaling, a mechanism for cellular stress resistance in long-lived mice.
AuthorsLeiser SF, Miller RA,
JournalMol Cell Biol
PubMed ID19933842
Transcriptional regulation of the antioxidant response element (ARE) by Nrf2 is important for the cellular adaptive response to toxic insults. New data show that primary skin-derived fibroblasts from the long-lived Snell dwarf mutant mouse, previously shown to be resistant to many toxic stresses, have elevated levels of Nrf2 and of ... 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
Activation of endothelial TRPV4 channels mediates flow-induced dilation in human coronary arterioles: role of Ca2+ entry and mitochondrial ROS signaling.
AuthorsBubolz AH, Mendoza SA, Zheng X, Zinkevich NS, Li R, Gutterman DD, Zhang DX,
JournalAm J Physiol Heart Circ Physiol
PubMed ID22140047
In human coronary arterioles (HCAs) from patients with coronary artery disease, flow-induced dilation is mediated by a unique mechanism involving the release of H(2)O(2) from the mitochondria of endothelial cells (ECs). How flow activates ECs to elicit the mitochondrial release of H(2)O(2) remains unclear. Here, we examined the role of ... More
Resveratrol protects mitochondria against oxidative stress through AMP-activated protein kinase-mediated glycogen synthase kinase-3beta inhibition downstream of poly(ADP-ribose)polymerase-LKB1 pathway.
AuthorsShin SM, Cho IJ, Kim SG,
JournalMol Pharmacol
PubMed ID19620254
Arachidonic acid (AA, a proinflammatory fatty acid) in combination with iron promotes excess reactive oxygen species (ROS) production and exerts a deleterious effect on mitochondria. We have shown previously that activation of AMP-activated protein kinase (AMPK) protects hepatocytes from AA + iron-induced apoptosis. Resveratrol, a polyphenol in grapes, has beneficial ... More
Yeast colony survival depends on metabolic adaptation and cell differentiation rather than on stress defense.
AuthorsCáp M, Váchová L, Palková Z,
JournalJ Biol Chem
PubMed ID19801643
Enzymes scavenging reactive oxygen species (ROS) are important for cell protection during stress and aging. A deficiency in these enzymes leads to ROS imbalance, causing various disorders in many organisms, including yeast. In contrast to liquid cultures, where fitness of the yeast population depends on its ROS scavenging capability, the ... More
Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin.
AuthorsHulsmans M, Van Dooren E, Mathieu C, Holvoet P,
JournalPLoS One
PubMed ID22393448
Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK)/NF?B pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR)-146b-5p inhibits NF?B-mediated inflammation ... 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
Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells.
AuthorsSaretzki G, Walter T, Atkinson S, Passos JF, Bareth B, Keith WN, Stewart R, Hoare S, Stojkovic M, Armstrong L, von Zglinicki T, Lako M,
JournalStem Cells
PubMed ID18055443
Evolutionary theory predicts that cellular maintenance, stress defense, and DNA repair mechanisms should be most active in germ line cells, including embryonic stem cells that can differentiate into germ line cells, whereas it would be energetically unfavorable to keep these up in mortal somatic cells. We tested this hypothesis by ... More
Caspase-cleaved tau expression induces mitochondrial dysfunction in immortalized cortical neurons: implications for the pathogenesis of Alzheimer disease.
AuthorsQuintanilla RA, Matthews-Roberson TA, Dolan PJ, Johnson GV,
JournalJ Biol Chem
PubMed ID19389700
In Alzheimer disease (AD) mitochondrial abnormalities occur early in the pathogenic process and likely play a significant role in disease progression. Tau is a microtubule-associated protein that is abnormally processed in AD, and a connection between tau pathology and mitochondrial impairment has been proposed. However, few studies have examined the ... More
Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures.
AuthorsChan DK, Miskimins WK,
JournalJ Ovarian Res
PubMed ID22781119
High mortality rates in ovarian cancer are largely a result of resistance to currently used chemotherapies. Expanding therapies with a variety of drugs has the potential to reduce this high mortality rate. Metformin and phenethyl isothiocyanate (PEITC) are both potentially useful in ovarian cancer, and they are particularly attractive because ... More
Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats.
AuthorsUngvari Z, Labinskyy N, Gupte S, Chander PN, Edwards JG, Csiszar A,
JournalAm J Physiol Heart Circ Physiol
PubMed ID18326800
Mitochondrial biogenesis is involved in the control of cell metabolism, signal transduction, and regulation of mitochondrial reactive oxygen species (ROS) production. Despite the central role of mitochondria in cellular aging and endothelial physiology, there are no studies extant investigating age-related alterations in mitochondrial biogenesis in blood vessels. Electronmicroscopy and confocal ... More
Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission.
AuthorsSharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, Morrow E, Ryan JJ, Archer SL,
Journal
PubMed ID24076965
Mitochondrial fission, regulated by dynamin-related protein-1 (Drp1), is a newly recognized determinant of mitochondrial function, but its contribution to left ventricular (LV) impairment following ischemia-reperfusion (IR) injury is unknown. We report that Drp1 activation during IR results in LV dysfunction and that Drp1 inhibition is beneficial. In both isolated neonatal ... More
Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo.
AuthorsMortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK,
JournalProc Natl Acad Sci U S A
PubMed ID20080761
Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by ... More
Estrogen Receptor {beta} as a Mitochondrial Vulnerability Factor.
AuthorsYang SH, Sarkar SN, Liu R, Perez EJ, Wang X, Wen Y, Yan LJ, Simpkins JW,
JournalJ Biol Chem
PubMed ID19189968
We recently demonstrated mitochondrial localization of estrogen receptor beta (ERbeta). We herein confirm the mitochondrial localization of ERbeta by the loss of mitochondrial ERbeta immunoreactivity in ERbeta knockdown cells. A phenotype change characterized as an increase in resistance to oxidative stressors is associated with ERbeta knockdown. ERbeta knockdown results in ... More
Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations.
Mutations of mitochondrial DNA are associated with a wide spectrum of disorders, primarily affecting the central nervous system and muscle function. The specific consequences of mitochondrial DNA mutations for neuronal pathophysiology are not understood. In order to explore the impact of mitochondrial mutations on neuronal biochemistry and physiology, we have ... More
PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death.
AuthorsGandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, Downward J, Latchman DS, Tabrizi SJ, Wood NW, Duchen MR, Abramov AY,
JournalMol Cell
PubMed ID19285945
Mutations in PINK1 cause autosomal recessive Parkinson's disease. PINK1 is a mitochondrial kinase of unknown function. We investigated calcium homeostasis and mitochondrial function in PINK1-deficient mammalian neurons. We demonstrate physiologically that PINK1 regulates calcium efflux from the mitochondria via the mitochondrial Na(+)/Ca(2+) exchanger. PINK1 deficiency causes mitochondrial accumulation of calcium, ... 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
Generation of reactive oxygen species by the mitochondrial electron transport chain.
AuthorsLiu Y, Fiskum G, Schubert D
JournalJ Neurochem
PubMed ID11948241
Generation of reactive oxygen species (ROS) by the mitochondrial electron transport chain (ETC), which is composed of four multiprotein complexes named complex I-IV, is believed to be important in the aging process and in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. Previous studies have identified the ubiquinone of ... More
Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation.
AuthorsEstévez AG, Spear N, Manuel SM, Radi R, Henderson CE, Barbeito L, Beckman JS
JournalJ Neurosci
PubMed ID9437014
Primary cultures of rat embryonic motor neurons deprived of brain-derived neurotrophic factor (BDNF) induce neuronal nitric oxide synthase (NOS) within 18 hr. Subsequently, >60% of the neurons undergo apoptosis between 18 and 24 hr after plating. Nitro-L-arginine and nitro-L-arginine methyl ester (L-NAME) prevented motor neuron death induced by trophic factor ... More
Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases.
AuthorsRego AC, Oliveira CR
JournalNeurochem Res
PubMed ID14570402
In recent years we have witnessed a major interest in the study of the role of mitochondria, not only as ATP producers through oxidative phosphorylation but also as regulators of intracellular Ca2+ homeostasis and endogenous producers of reactive oxygen species (ROS). Interestingly, the mitochondria have been also implicated as central ... More
Nitric oxide and reactive oxygen species in Parkinson's disease.
AuthorsTieu K, Ischiropoulos H, Przedborski S
JournalIUBMB Life
PubMed ID12938735
Parkinson's disease is a neurodegenerative disorder of unknown pathogenesis. Oxidative stress has been proposed as one of several pathogenic hypotheses. Evidence for the participation of oxidative processes in the pathogenesis of Parkinson's disease have been obtained in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model by the use of genetically altered mice. MPTP administration ... More
Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I.
AuthorsIuso A, Scacco S, Piccoli C, Bellomo F, Petruzzella V, Trentadue R, Minuto M, Ripoli M, Capitanio N, Zeviani M, Papa S
JournalJ Biol Chem
PubMed ID16478720
The pathogenic mechanism of a G44A nonsense mutation in the NDUFS4 gene and a C1564A mutation in the NDUFS1 gene of respiratory chain complex I was investigated in fibroblasts from human patients. As previously observed the NDUFS4 mutation prevented complete assembly of the complex and caused full suppression of the ... More
Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita(+/Ins2)-derived ß-cells.
AuthorsMitchell T, Johnson MS, Ouyang X, Chacko BK, Mitra K, Lei X, Gai Y, Moore DR, Barnes S, Zhang J, Koizumi A, Ramanadham S, Darley-Usmar VM
Journal
PubMed ID23820623
Insulin release from pancreatic ß-cells plays a critical role in blood glucose homeostasis, and ß-cell dysfunction leads to the development of diabetes mellitus. In cases of monogenic type 1 diabetes mellitus (T1DM) that involve mutations in the insulin gene, we hypothesized that misfolding of insulin could result in endoplasmic reticulum ... More
Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression.
AuthorsPiacenza L, Irigoín F, Alvarez MN, Peluffo G, Taylor MC, Kelly JM, Wilkinson SR, Radi R
JournalBiochem J
PubMed ID17168856
Trypanosoma cruzi undergo PCD (programmed cell death) under appropriate stimuli, the mechanisms of which remain to be established. In the present study, we show that stimulation of PCD in T. cruzi epimastigotes by FHS (fresh human serum) results in rapid (<1 h) externalization of phosphatidylserine and depletion of the low ... More
Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation.
AuthorsAbramov AY, Scorziello A, Duchen MR
JournalJ Neurosci
PubMed ID17267568
Ischemia is a major cause of brain damage, and patient management is complicated by the paradoxical injury that results from reoxygenation. We have now explored the generation of reactive oxygen species (ROS) in hippocampal and cortical neurons in culture in response to oxygen and glucose deprivation or metabolic inhibition and ... More
Effects of extensively oxidized low-density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells.
Atherosclerotic cardiovascular disease is the leading cause of mortality in the Western world. Dysfunction of the mitochondrial respiratory chain and overproduction of reactive oxygen species (ROS) are associated with atherosclerosis and cardiovascular disease. Oxidation increases the atherogenecity of LDL. Oxidized LDL may be apoptotic or nonapoptotic for vascular endothelial cells ... More
Energy Metabolism and Mitochondrial Superoxide Anion Production in Pre-symptomatic Striatal Neurons Derived from Human-Induced Pluripotent Stem Cells Expressing Mutant Huntingtin.
AuthorsHamilton J, Brustovetsky T, Sridhar A, Pan Y, Cummins TR, Meyer JS, Brustovetsky N
JournalMol Neurobiol
PubMed ID31435904
'In the present study, we investigated whether mutant huntingtin (mHTT) impairs mitochondrial functions in human striatal neurons derived from induced pluripotent stem cells (iPSCs). Striatal neurons and astrocytes derived from iPSCs from unaffected individuals (Ctrl) and Huntington''s disease (HD) patients with HTT gene containing increased number of CAG repeats were ... More
Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice.
AuthorsMcQuade RM, Carbone SE, Stojanovska V, Rahman A, Gwynne RM, Robinson AM, Goodman CA, Bornstein JC, Nurgali K
JournalBr J Pharmacol
PubMed ID27714760
'Oxaliplatin is a platinum-based chemotherapeutic drug used as a first-line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side-effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic ... More
Lamotrigine Attenuates Proteasome Inhibition-Induced Apoptosis by Suppressing the Activation of the Mitochondrial Pathway and the Caspase-8- and Bid-Dependent Pathways.
AuthorsNam YJ, Kim A, Lee MS, Shin YK, Sohn DS, Lee CS
JournalNeurochem Res
PubMed ID27230883
'Proteasome impairment has been shown to be involved in neuronal degeneration. Antiepileptic lamotrigine has been demonstrated to have a neuroprotective effect. However, the effect of lamotrigine on the proteasome inhibition-induced neuronal cell death has not been studied. Therefore, we assessed the effect of lamotrigine on the proteasome inhibition-induced neuronal cell ... More
Synthesis of Pegylated Manganese Protoporphyrin as a Catalase Mimic and Its Therapeutic Application to Acetaminophen-Induced Acute Liver Failure.
AuthorsZhang T, Fang J, Tsutsuki H, Ono K, Islam W, Sawa T
JournalBiol Pharm Bull
PubMed ID31257295
'Metalloporphyrin derivatives have been investigated for their therapeutic potential for oxidative stress-related diseases because of their scavenging of reactive oxygen species (ROS). Here, we describe the synthesis, physicochemical properties, and ROS-scavenging activities of one such derivative-polyethylene glycol (PEG)-conjugated manganese protoporphyrin (PEG-MnPP). Carboxyl groups of the protoporphyrin ring at the C6 ... More
Budesonide and Poractant Alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway.
AuthorsDu FL, Dong WB, Zhang C, Li QP, Kang L, Lei XP, Guo L, Zhai XS
JournalEur Rev Med Pharmacol Sci
PubMed ID31858575
'This study aimed to evaluate effect of budesonide combining Poractant Alfa on preventing bronchopulmonary dysplasia (BPD).'
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS.
Authors
JournalCell
PubMed ID33031745
NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages.
Authors
JournalNat Med
PubMed ID27455510
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.
Authors
JournalCell
PubMed ID27984723
A Cellular Mechanism to Detect and Alleviate Reductive Stress.
Authors
JournalCell
PubMed ID32941802
Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice.
Authors
JournalNat Med
PubMed ID26752519
M. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity.
Authors
JournalCell
PubMed ID33125891
Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output.
Authors
JournalCell
PubMed ID32931733
FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.
Authors
JournalCell
PubMed ID31978345
Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation.
Authors
JournalCell
PubMed ID29033131
A Compendium of Genetic Modifiers of Mitochondrial Dysfunction Reveals Intra-organelle Buffering.
Authors
JournalCell
PubMed ID31730859
Novel CHOP activator LGH00168 induces necroptosis in A549 human lung cancer cells via ROS-mediated ER stress and NF-?B inhibition.
AuthorsMa YM, Peng YM, Zhu QH, Gao AH, Chao B, He QJ, Li J, Hu YH, Zhou YB
JournalActa Pharmacol Sin
PubMed ID27264312
C/EBP homologous protein (CHOP) is a transcription factor that is activated at multiple levels during ER stress and plays an important role in ER stress-induced apoptosis. In this study we identified a novel CHOP activator, and further investigated its potential to be a therapeutic agent for human lung cancer. ... More
Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways.
AuthorsWang K, Fu XT, Li Y, Hou YJ, Yang MF, Sun JY, Yi SY, Fan CD, Fu XY, Zhai J, Sun BL
JournalNeurochem Res
PubMed ID26846141
Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction ... More