Rho proteins, members of the Ras superfamily of GTPases, are critical elements in signal transduction pathways governing cell proliferation and cell death. Different members of the family of human Rho GTPases, including RhoA, RhoC, and Rac1, participate in the regulation of apoptosis in response to cytokines and serum deprivation in ... More
Large-scale chemical dissection of mitochondrial function.
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
Authors
Journal
PubMed ID10891486
Mitochondria--potential role in cell life and death.
AuthorsGriffiths EJ
JournalCardiovascular research
PubMed ID10727650
The mitochondrial death/life regulator in apoptosis and necrosis.
AuthorsKroemer G,Dallaporta B,Resche-Rigon M
JournalAnnual review of physiology
PubMed ID9558479
Both physiological cell death (apoptosis) and, in some cases, accidental cell death (necrosis) involve a two-step process. At a first level, numerous physiological and some pathological stimuli trigger an increase in mitochondrial membrane permeability. The mitochondria release apoptogenic factors through the outer membrane and dissipate the electrochemical gradient of the ... More
Seminal plasma addition attenuates the dilution effect in bovine sperm.
Dilution of semen to low cell numbers/dose can result in a bull-dependent reduction in the post-thaw viability of cryopreserved bovine spermatozoa. It is possible that essential seminal plasma components are lacking at the greater dilution rates, thereby contributing to the deleterious effects of semen dilution. Ejaculates of 6 Holstein bulls ... More
Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine.
AuthorsRama Rao KV, Jayakumar AR, Norenberg MD
JournalNeurochem Int
PubMed ID12742099
Ammonia is a toxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE), and astrocytes appear to be the principal target of ammonia toxicity. Glutamine, a byproduct of ammonia metabolism, has been implicated in some of the deleterious effects of ammonia on the CNS. We have recently ... More
Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death.
AuthorsOgbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG
JournalCancer Res
PubMed ID15087400
Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rates and extended treatment schedules. Here, we describe the preclinical ... More
Sevoflurane depolarizes pre-synaptic mitochondria in the central nervous system.
BACKGROUND: Volatile anaesthetics protect the heart from ischaemic injury by activating mitochondrial signalling pathways. The aim of this study was to test whether sevoflurane, which is increasingly used in neuroanaesthesia, affects mitochondrial function in the central nervous system by altering the mitochondrial membrane potential (DeltaPsi(m)). METHODS: In order to correlate ... More
Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.
AuthorsHori O, Ichinoda F, Tamatani T, Yamaguchi A, Sato N, Ozawa K, Kitao Y, Miyazaki M, Harding HP, Ron D, Tohyama M, M Stern D, Ogawa S
JournalJ Cell Biol
PubMed ID12082077
'The rat homologue of a mitochondrial ATP-dependent protease Lon was cloned from cultured astrocytes exposed to hypoxia. Expression of Lon was enhanced in vitro by hypoxia or ER stress, and in vivo by brain ischemia. These observations suggested that changes in nuclear gene expression (Lon) triggered by ER stress had ... More
Tamoxifen but not 4-hydroxytamoxifen initiates apoptosis in p53(-) normal human mammary epithelial cells by inducing mitochondrial depolarization.
AuthorsDietze EC, Caldwell LE, Grupin SL, Mancini M, Seewaldt VL
JournalJ Biol Chem
PubMed ID11094056
'Despite the widespread clinical use of tamoxifen as a breast cancer prevention agent, the molecular mechanism of tamoxifen chemoprevention is poorly understood. Abnormal expression of p53 is felt to be an early event in mammary carcinogenesis. We developed an in vitro model of early breast cancer prevention to investigate how ... More
Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis.
AuthorsMartinvalet D, Zhu P, Lieberman J
JournalImmunity
PubMed ID15780992
'Granzyme A (GzmA) triggers cell death with apoptotic features by targeting the endoplasmic reticulum-associated SET complex, which contains the GzmA-activated DNase NM23-H1, its inhibitor SET, and Ape1. The SET complex was postulated to translocate to the nucleus in response to oxidative stress and participate in its repair. Because mitochondrial damage ... More
Tissue transglutaminase is a multifunctional BH3-only protein.
AuthorsRodolfo C, Mormone E, Matarrese P, Ciccosanti F, Farrace MG, Garofano E, Piredda L, Fimia GM, Malorni W, Piacentini M
JournalJ Biol Chem
PubMed ID15485857
'Tissue transglutaminase (TG2) protein accumulates to high levels in cells during early stages of apoptosis both in vivo and in vitro. The analysis of the TG2 primary sequence showed the presence of an eight amino acid domain, sharing 70% identity with the Bcl-2 family BH3 domain. Cell-permeable peptides, mimicking the ... More
Titrating the effects of mitochondrial complex I impairment in the cell physiology.
AuthorsBarrientos A, Moraes CT
JournalJ Biol Chem
PubMed ID10347173
'The mitochondrial oxidative phosphorylation system consists of five multimeric enzymes (complexes I-V). NADH dehydrogenase or complex I (CI) is affected in most of the mitochondrial diseases and in some neurodegenerative disorders. We have studied the physiological consequences of a partial CI inhibition at the cellular level. We used a genetic ... More
Engagement of CD4 before TCR triggering regulates both Bax- and Fas (CD95)-mediated apoptosis.
AuthorsSomma F, Tuosto L, Gilardini Montani MS, Di Somma MM, Cundari E, Piccolella E
JournalJ Immunol
PubMed ID10799864
'In the present study, we have aimed at clarifying the CD4-dependent molecular mechanisms that regulate human memory T cell susceptibility to both Fas (CD95)-dependent and Bcl-2-dependent apoptotic pathways following antigenic challenge. To address this issue, we used an experimental system of viral and alloantigen-specific T cell lines and clones and ... More
Cytochrome c-mediated apoptosis in cells lacking mitochondrial DNA. Signaling pathway involving release and caspase 3 activation is conserved.
AuthorsJiang S, Cai J, Wallace DC, Jones DP
JournalJ Biol Chem
PubMed ID10514472
'Mitochondria serve as a pivotal component of the apoptotic cell death machinery. However, cells that lack mitochondrial DNA (rho(0) cells) retain apparently normal apoptotic signaling. In the present study, we examined mitochondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with staurosporine. Immunohistochemistry revealed that rho(0) cells maintained a normal ... More
Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria.
'Mitochondrial physiology is disrupted in either apoptosis or necrosis. Here, we report that a wide variety of apoptotic and necrotic stimuli induce progressive mitochondrial swelling and outer mitochondrial membrane rupture. Discontinuity of the outer mitochondrial membrane results in cytochrome c redistribution from the intermembrane space to the cytosol followed by ... More
In vitro studies on the toxicity of isoniazid in different cell lines.
AuthorsSchwab CE, Tuschl H
JournalHum Exp Toxicol
PubMed ID14686483
'The aim of the present study was to investigate in vitro the mechanism of toxicity of isoniazid (= INH), the drug most widely used for treatment of tuberculosis. The human hepatoma line HepG2, the human lymphoblastoid line AHH-1 and the murine lymphoma cells YAC-1 were used as test systems. Active ... More
Differential gel electrophoresis and transgenic mitochondrial calcium reporters demonstrate spatiotemporal filtering in calcium control of mitochondria.
AuthorsTerhzaz S, Southall TD, Lilley KS, Kean L, Allan AK, Davies SA, Dow JA
JournalJ Biol Chem
PubMed ID16670086
'Mitochondria must adjust both their intracellular location and their metabolism in order to balance their output to the needs of the cell. Here we show by the proteomic technique of time series difference gel electrophoresis that a major result of neuroendocrine stimulation of the Drosophila renal tubule is an extensive ... More
Lead and calcium produce rod photoreceptor cell apoptosis by opening the mitochondrial permeability transition pore.
AuthorsHe L, Poblenz AT, Medrano CJ, Fox DA
JournalJ Biol Chem
PubMed ID10766853
'Calcium overload is suggested to play a fundamental role in the process of rod apoptosis in chemical-induced and inherited retinal degenerations. However, this hypothesis has not been tested directly. We developed an in vitro model utilizing isolated rat retinas to determine the mechanisms underlying Ca(2+)- and/or Pb(2+)-induced retinal degeneration. Confocal ... More
Vitamin D enhances caspase-dependent and -independent TNFalpha-induced breast cancer cell death: The role of reactive oxygen species and mitochondria.
AuthorsWeitsman GE, Ravid A, Liberman UA, Koren R
JournalInt J Cancer
PubMed ID12800192
'Calcitriol, the hormonal form of vitamin D, potentiates the activity of some common anticancer drugs and agents of the anticancer immune system, including tumor necrosis factor alpha (TNFalpha). TNFalpha-induced cytotoxicity is due to both caspase-dependent and -independent pathways. Cotreatment with calcitriol enhanced both modes of TNFalpha-induced death in MCF-7 breast ... More
Poly(ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition.
AuthorsAlano CC, Ying W, Swanson RA
JournalJ Biol Chem
PubMed ID14960594
'Extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1) by DNA damage is a major cause of caspase-independent cell death in ischemia and inflammation. Here we show that NAD(+) depletion and mitochondrial permeability transition (MPT) are sequential and necessary steps in PARP-1-mediated cell death. Cultured mouse astrocytes were treated with the cytotoxic concentrations ... More
Effects of oxidants and glutamate receptor activation on mitochondrial membrane potential in rat forebrain neurons.
AuthorsScanlon JM, Reynolds IJ
JournalJ Neurochem
PubMed ID9832137
'Both glutamate and reactive oxygen species have been implicated in excitotoxic neuronal injury, and mitochondria may play a key role in the mediation of this process. In this study, we examined whether glutamate-receptor stimulation and oxidative stress interact to affect the mitochondrial membrane potential (delta psi). We measured delta psi ... More
Mechanisms of mitochondria-neurofilament interactions.
'Mitochondria are localized to regions of the cell where ATP consumption is high and are dispersed according to changes in local energy needs. In addition to motion directed by molecular motors, mitochondrial distribution in neuronal cells appears to depend on the docking of mitochondria to microtubules and neurofilaments. We examined ... More
A new method for in vitro detection of microbially produced mitochondrial toxins.
AuthorsHoornstra D, Andersson MA, Mikkola R, Salkinoja-Salonen MS
JournalToxicol In Vitro
PubMed ID14599472
'Sperm motility inhibition assay, earlier shown valuable for the detection of food poisoning non-protein toxins of Bacillus species was developed into an assay useful for specific detection of mitochondria damaging toxins. This was done by assessing the dissipation of the mitochondrial inner membrane transmembrane potential, Deltapsim under conditions where the ... More
The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosis.
AuthorsFossati G, Moulding DA, Spiller DG, Moots RJ, White MR, Edwards SW
JournalJ Immunol
PubMed ID12574365
'It is commonly assumed that human neutrophils possess few, if any, functional mitochondria and that they do not depend on these organelles for cell function. We have used the fluorescent mitochondrial indicators, JC-1, MitoTracker Red, and dihydrorhodamine 123 to show that live neutrophils possess a complex mitochondrial network that extends ... More
Rhodamine-123 staining in hematopoietic stem cells of young mice indicates mitochondrial activation rather than dye efflux.
AuthorsKim M, Cooper DD, Hayes SF, Spangrude GJ
JournalBlood
PubMed ID9596656
'Low-intensity fluorescence of rhodamine-123 (Rh-123) discriminates a quiescent hematopoietic stem cell (HSC) population in mouse bone marrow, which provides stable, long-term hematopoiesis after transplantation. Rh-123 labels mitochondria with increasing intensity proportional to cellular activation, however the intensity of staining also correlates with the multidrug resistance (MDR) phenotype, as Rh-123 is ... More
Flex-Hets differentially induce apoptosis in cancer over normal cells by directly targeting mitochondria.
AuthorsLiu T, Hannafon B, Gill L, Kelly W, Benbrook D
JournalMol Cancer Ther
PubMed ID17575110
'Flex-Het drugs induce apoptosis in multiple types of cancer cells, with little effect on normal cells. This apoptosis occurs through the intrinsic mitochondrial pathway accompanied by generation of reactive oxygen species (ROS). The objective of this study was to determine if direct or indirect targeting of mitochondria is responsible for ... More
Nitric oxide-dependent mitochondrial biogenesis generates Ca2+ signaling profile of lupus T cells.
AuthorsNagy G, Barcza M, Gonchoroff N, Phillips PE, Perl A
JournalJ Immunol
PubMed ID15356113
'Abnormal T cell activation and cell death underlie the pathology of systemic lupus erythematosus. Although mitochondrial hyperpolarization (MHP) represents an early and reversible checkpoint of T cell activation and apoptosis, lupus T cells exhibit persistent MHP. NO has recently been recognized as a key signal of mitochondrial biogenesis and mediator ... More
p38 mitogen-activated protein kinase mediates bid cleavage, mitochondrial dysfunction, and caspase-3 activation during apoptosis induced by singlet oxygen but not by hydrogen peroxide.
AuthorsZhuang S, Demirs JT, Kochevar IE
JournalJ Biol Chem
PubMed ID10837470
'p38 mitogen-activated protein kinase is activated and involved in cleavage of caspase-3 during apoptosis induced by a number of stimuli. However, the signaling events triggered by p38 that result in caspase-3 activation are still unknown. In human leukemia cells, two reactive oxygen species, singlet oxygen and hydrogen peroxide (H(2)O(2)), selectively ... More
In vivo VL-targeted activation-induced apoptotic supraclonal deletion by a microbial B cell toxin.
AuthorsGoodyear CS, Narita M, Silverman GJ
JournalJ Immunol
PubMed ID14978088
'To interfere with host immune responses, some microbial pathogens produce proteins with the properties of superantigens, which can interact via conserved V region framework subdomains of the Ag receptors of lymphocytes rather than the complementarity-determining region involved in the binding of conventional Ags. In recent studies, we have elucidated how ... More
Evaluation of fluorescent dyes for the detection of mitochondrial membrane potential changes in cultured cardiomyocytes.
AuthorsMathur A, Hong Y, Kemp BK, Barrientos AA, Erusalimsky JD
JournalCardiovasc Res
PubMed ID10727661
'OBJECTIVE: Maintenance of the mitochondrial membrane potential (Deltapsim) is fundamental for the normal performance and survival of cells such as cardiomyocytes, that have a high energy requirement. Measurement of Deltapsim is therefore essential in order to develop an understanding of the molecular mechanisms controlling cardiomyocyte function. Here we have evaluated ... More
Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome.
AuthorsTakatani T, Takahashi K, Uozumi Y, Shikata E, Yamamoto Y, Ito T, Matsuda T, Schaffer SW, Fujio Y, Azuma J
JournalAm J Physiol Cell Physiol
PubMed ID15253891
'Cardiomyocyte apoptosis contributes to cell death during myocardial infarction. One of the factors that regulate the degree of apoptosis during ischemia is the amino acid taurine. To study the mechanism underlying the beneficial effect of taurine, we examined the interaction between taurine and mitochondria-mediated apoptosis using a simulated ischemia model ... More
Enantio-specific induction of apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells: suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine.
AuthorsMaruyama W, Boulton AA, Davis BA, Dostert P, Naoi M
JournalJ Neural Transm
PubMed ID11261742
'Endogenous N-methyl(R)salsolinol, which caused parkinsonism in rats by injection in the striatum, was found to induce apoptosis in dopaminergic neuroblastoma SH-SY5Y cells. After 12-h incubation with 500[microM N-methyl(R)salsolinol, almost all the cells died with apoptosis and necrotic cell death was negligible. N-Methyl(R)salsolinol was much more potent to induce apoptosis than ... More
Flow cytometric measurement of mitochondrial mass and function: a novel method for assessing chemoresistance.
AuthorsMancini M, Sedghinasab M, Knowlton K, Tam A, Hockenbery D, Anderson BO
JournalAnn Surg Oncol
PubMed ID9607633
'BACKGROUND: Chemotherapeutic agents induce apoptosis in cancer cells. Drugs failing to induce apoptosis are likely to have decreased clinical efficacy. We hypothesize that (1) chemotherapeutic agents induce mitochondrial changes and apoptosis through mechanisms associated with reactive oxidant species production; (2) the anti-apoptotic protein Bcl-2 prevents drug-induced mitochondrial changes, reactive oxygen ... More
Dynamical change of mitochondrial DNA induced in the living cell by perturbing the electrochemical gradient.
AuthorsCoppey-Moisan M, Brunet AC, Morais R, Coppey J
JournalBiophys J
PubMed ID8913573
'Digital-imaging microscopy was used in conditions that allowed the native state to be preserved and hence fluorescence variations of specific probes to be followed in the real time of living mammalian cells. Ethidium bromide was shown to enter into living cells and to intercalate stably into mitochondrial DNA (mtDNA), giving ... More
Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines.
AuthorsLazzè MC, Savio M, Pizzala R, Cazzalini O, Perucca P, Scovassi AI, Stivala LA, Bianchi L
JournalCarcinogenesis
PubMed ID15016660
'To investigate the mechanistic basis for the biological properties of anthocyanins, two aglycone anthocyanins [delphinidin (DY) and cyanidin (CY)] were used to examine their effects on cell cycle progression and on induction of apoptosis in human cancer cells (uterine carcinoma and colon adenocarcinoma cells) and in normal human fibroblasts. These ... More
The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome.
'The yeast open reading frames YOL027 and YPR125 and their orthologs in various eukaryotes encode proteins with a single predicted trans-membrane domain ranging in molecular mass from 45 to 85 kDa. Hemizygous deletion of their human homolog LETM1 is likely to contribute to the Wolf-Hirschhorn syndrome phenotype. We show here ... More
Effects of heat shock on the functional morphology of cell organelles observed by video-enhanced microscopy.
'In living astrocytes and MDCK cells we observed morphological phenomena during and after heat shock (HS) utilizing our new perfusable microchamber system, which monitors pH, pO(2), pCO(2), and temperature. By means of electronic light microscopy and confocal laser scanning microscopy, mitochondria were demonstrated to swell and to reduce their motility. ... More
Cocaine-mediated enhancement of Tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor.
AuthorsAksenov MY, Aksenova MV, Nath A, Ray PD, Mactutus CF, Booze RM
JournalNeurotoxicology
PubMed ID16386305
'It is becoming widely accepted that psychoactive drugs can significantly alter the progression of neuropathological changes in the HIV-infected brain. The use of cocaine can aggravate the neurotoxic effects of HIV-1 proteins such as HIV-1 transactivating protein Tat and virus'' envelope protein gp120. HIV-1 Tat is believed to play an ... More
Tumor apoptosis induced by epoxide-containing piperazines, a new class of anti-cancer agents.
'PURPOSE: The overall purpose of this study was to determine the potential efficacy of epoxide-containing piperazines as a new class of anti-cancer agents. Two representative compounds, specifically NCO-700, a 4-trimethoxyphenyl-substituted epoxide-piperazine, and TOP-008, a 4-phenylpropenyl-substituted epoxide-piperazine were tested in cytotoxic assays with human breast and prostate cancer cell lines. A ... More
CCL5-CCR5-mediated apoptosis in T cells: Requirement for glycosaminoglycan binding and CCL5 aggregation.
AuthorsMurooka TT, Wong MM, Rahbar R, Majchrzak-Kita B, Proudfoot AE, Fish EN
JournalJ Biol Chem
PubMed ID16807236
'CCL5 (RANTES (regulated on activation normal T cell expressed and secreted)) and its cognate receptor, CCR5, have been implicated in T cell activation. CCL5 binding to glycosaminoglycans (GAGs) on the cell surface or in extracellular matrix sequesters CCL5, thereby immobilizing CCL5 to provide the directional signal. In two CCR5-expressing human ... More
Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway.
AuthorsRuan Q, Lesort M, MacDonald ME, Johnson GV
JournalHum Mol Genet
PubMed ID14962977
'Extensive striatal neuronal loss occurs in Huntington''s disease (HD), which is caused by an expanded polyglutamine tract in huntingtin (htt). Evidence suggests that mutant htt directly or indirectly compromises mitochondrial function, contributing to the neuronal loss. To determine the role of compromised mitochondrial function in the neuronal cell death in ... More
Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency.
AuthorsLópez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R
JournalProc Natl Acad Sci U S A
PubMed ID16446459
'Age-related accumulation of cellular damage and death has been linked to oxidative stress. Calorie restriction (CR) is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in a variety of species. Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative ... More
Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of alpha-ketoglutarate dehydrogenase.
AuthorsChinopoulos C, Tretter L, Adam-Vizi V
JournalJ Neurochem
PubMed ID10386974
'Mitochondrial membrane potential (delta psi(m)) was determined in intact isolated nerve terminals using the membrane potential-sensitive probe JC-1. Oxidative stress induced by H2O2 (0.1-1 mM) caused only a minor decrease in delta psi(m). When complex I of the respiratory chain was inhibited by rotenone (2 microM), delta psi(m) was unaltered, ... More
JNK regulates HIPK3 expression and promotes resistance to Fas-mediated apoptosis in DU 145 prostate carcinoma cells.
AuthorsCurtin JF, Cotter TG
JournalJ Biol Chem
PubMed ID14766760
'Elevated endogenous JNK activity and resistance to Fas receptor-mediated apoptosis have recently been implicated in progression of prostate cancer and can promote resistance to apoptosis in response to chemotherapeutic drugs. In addition, JNK has been demonstrated to promote transformation of epithelial cells by increasing both proliferation and survival. Although numerous ... More
Stimulation-evoked increases in cytosolic [Ca(2+)] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent.
AuthorsDavid G, Barrett EF
JournalJ Neurosci
PubMed ID11007886
'Increases in cytosolic [Ca(2+)] evoked by trains of action potentials (20-100 Hz) were recorded from mouse and lizard motor nerve terminals filled with a low-affinity fluorescent indicator, Oregon Green BAPTA 5N. In mouse terminals at near-physiological temperatures (30-38 degrees C), trains of action potentials at 25-100 Hz elicited increases in ... More
Assessment of equine sperm mitochondrial function using JC-1.
AuthorsGravance CG, Garner DL, Baumber J, Ball BA
JournalTheriogenology
PubMed ID10968415
'The fluorescent carbocyanine dye, JC-1, labels mitochondria with high membrane potential orange and mitochondria with low membrane potential green. Evaluation of mitochondrial membrane potential with JC-1 has been used in a variety of cell types, including bull spermatozoa; however, JC-1 staining has not yet been reported for equine spermatozoa. The ... More
Inner mitochondrial membrane potential (DeltaPsim), cytoplasmic ATP content and free Ca2+ levels in metaphase II mouse oocytes.
AuthorsVan Blerkom J, Davis P, Alexander S
JournalHum Reprod
PubMed ID14585897
'BACKGROUND: The relative magnitude of the inner mitochondrial membrane potential (DeltaPsim) has been suggested to indicate the competence of mammalian gametes and early embryos. This study examined the response of cultured somatic cells and mouse oocytes to inhibitors and conditions that affect DeltaPsim or metabolism, or both, and measured treatment-specific ... More
CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture.
AuthorsKirshner J, Chen CJ, Liu P, Huang J, Shively JE
JournalProc Natl Acad Sci U S A
PubMed ID12522268
'In a 3D model of breast morphogenesis, CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) plays an essential role in lumen formation in a subline of the nonmalignant human breast cell line (MCF10A). We show that mammary carcinoma cells (MCF7), which do not express CEACAM1 or form lumena when grown in ... More
Saikosaponin-d Enhances the Anticancer Potency of TNF-a via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells.
AuthorsWong VK, Zhang MM, Zhou H, Lam KY, Chan PL, Law CK, Yue PY, Liu L,
JournalEvid Based Complement Alternat Med
PubMed ID23573150
'Tumor necrosis factor-alpha (TNF- a ) was reported as anticancer therapy due to its cytotoxic effect against an array of tumor cells. However, its undesirable responses of TNF- a on activating NF- ? B signaling and pro-metastatic property limit its clinical application in treating cancers. Therefore, sensitizing agents capable of ... More
Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death.
AuthorsClarke MC, Savill J, Jones DB, Noble BS, Brown SB
JournalJ Cell Biol
PubMed ID12591916
'Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be ... More
Reduced Ca2+ uptake by mitochondria in pyruvate dehydrogenase-deficient human diploid fibroblasts.
AuthorsPadua RA, Baron KT, Thyagarajan B, Campbell C, Thayer SA
JournalAm J Physiol
PubMed ID9530092
'Physiological and pathological Ca2+ loads are thought to be taken up by mitochondria via a process dependent on aerobic metabolism. We sought to determine whether human diploid fibroblasts from a patient with an inherited defect in pyruvate dehydrogenase (PDH) exhibit a decreased ability to sequester cytosolic Ca2+ into mitochondria. Mobilization ... More
Mitochondrial permeability transition and swelling can occur reversibly without inducing cell death in intact human cells.
AuthorsMinamikawa T, Williams DA, Bowser DN, Nagley P
JournalExp Cell Res
PubMed ID9882512
'Severe disruption of mitochondrial function is generally considered to provide a powerful trigger for apoptosis in mammalian cells. We report here that intact cells may undergo the mitochondrial permeability transition and mitochondria swell in a fully reversible manner, without inducing cell death. Cultured human osteosarcoma cells (143B TK-) stained with ... More
Apoptotic activity in stored human platelets.
AuthorsPerrotta PL, Perrotta CL, Snyder EL
JournalTransfusion
PubMed ID12662287
'BACKGROUND: Platelets possess some of the machinery required for apoptotic cell death. However, disruption of mitochondria function, implicated in several models of cell death, has not been extensively studied in platelets. Mitochondrial viability and several other measures of apoptotic death in stored and experimentally stressed platelets were evaluated. MATERIALS AND ... More
Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
AuthorsGalluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Castedo M, Cidlowski JA, Ciechanover A, Cohen GM, De Laurenzi V, De Maria R, Deshmukh M, Dynlacht BD, El-Deiry WS, Flavell RA, Fulda S, Garrido C, Golstein P, Gougeon ML, Green DR, Gronemeyer H, Hajnóczky G, Hardwick JM, Hengartner MO, Ichijo H, Jäättelä M, Kepp O, Kimchi A, Klionsky DJ, Knight RA, Kornbluth S, Kumar S, Levine B, Lipton SA, Lugli E, Ma
JournalCell Death Differ
PubMed ID19373242
'Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, ... 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
Methods for the assessment of mitochondrial membrane permeabilization in apoptosis.
AuthorsGalluzzi L, Zamzami N, de La Motte Rouge T, Lemaire C, Brenner C, Kroemer G
JournalApoptosis
PubMed ID17294081
'Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable ... More
Increased [Mg2+]o reduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation.
AuthorsSharikabad MN, Ostbye KM, Brørs O
JournalAm J Physiol Heart Circ Physiol
PubMed ID11668073
'Increase in extracellular Mg2+ concentration ([Mg2+]o) reduces Ca2+ accumulation during reoxygenation of hypoxic cardiomyocytes and exerts protective effects. The aims of the present study were to investigate the effect of increased [Mg(2+)](o) on Ca2+ influx and efflux, free cytosolic Ca2+ ([Ca2+]i) and Mg2+ concentrations ([Mg2+]i), Ca2+ accumulation in the presence ... More
Stimulation of the pentose phosphate pathway and glutathione levels by dehydroascorbate, the oxidized form of vitamin C.
AuthorsPuskas F, Gergely P, Banki K, Perl A
JournalFASEB J
PubMed ID10877828
'Ascorbic acid, or vitamin C, generally functions as an antioxidant by directly reacting with reactive oxygen intermediates and has a vital role in defenses against oxidative stress. However, ascorbic acid also has pro-oxidant properties and may cause apoptosis of lymphoid and myeloid cells. The present study shows that dehydroascorbate, the ... More
Relocalization of cathepsin D and cytochrome c early in apoptosis revealed by immunoelectron microscopy.
AuthorsRoberg K
JournalLab Invest
PubMed ID11232636
'Cathepsin D was translocated from lysosomal structures to the cytosol in primary cultures of neonatal rat cardiomyocytes exposed to oxidative stress, and these cells underwent apoptotic death during subsequent incubation. Temporal aspects of cathepsin D relocalization, cytochrome c release, and decrease in mitochondrial transmembrane potential (delta psi(m)) were studied in ... 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
Pseudoapoptosis induced by brief activation of ATP-gated P2X7 receptors.
AuthorsMackenzie AB, Young MT, Adinolfi E, Surprenant A
JournalJ Biol Chem
PubMed ID15994333
'P2X7 receptors are ATP-gated ion channels primarily expressed on antigen-presenting immune cells where they play a role in the acute inflammatory response. These ion channels couple not only to influx of cations, including calcium, but also to rapid alterations in cell morphology (membrane blebbing, phosphatidylserine exposure, microvesicle shedding). These features ... More
Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro.
AuthorsCarlsson C, Borg LA, Welsh N
JournalEndocrinology
PubMed ID10433196
'The aim of the present investigation was to study whether prolonged exposure of isolated rat islets to the long chain fatty acid sodium palmitate leads to uncoupling of respiration. It was found that culture of islets in the presence of palmitate abolished glucose-sensitive insulin release and decreased insulin contents. This ... More
Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule.
AuthorsCarrero JA, Calderon B, Unanue ER
JournalJ Immunol
PubMed ID15067065
'Infection of mice with Listeria monocytogenes caused marked lymphocyte apoptosis in the white pulp of the spleen on day 2 postinfection. We prove in this study that listeriolysin O (LLO), a pore-forming molecule and a major virulence factor of Listeria, could directly induce murine lymphocyte apoptosis both in vivo and ... More
Functional reconstitution of bacterially expressed human potassium channels in proteoliposomes: membrane potential measurements with JC-1 to assay ion channel activity.
AuthorsChanda B, Mathew MK
JournalBiochim Biophys Acta
PubMed ID9889332
'Structure-function studies on ion channels have been greatly facilitated by the cloning of cDNAs from a variety of sources. However, obtaining detailed structural information on these proteins requires overexpression, purification and reconstitution in a functionally competent form. In this communication, we report on the functional reconstitution of a human potassium ... 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
Deficiency of the cyclin kinase inhibitor p21(WAF-1/CIP-1) promotes apoptosis of activated/memory T cells and inhibits spontaneous systemic autoimmunity.
AuthorsLawson BR, Baccala R, Song J, Croft M, Kono DH, Theofilopoulos AN
JournalJ Exp Med
PubMed ID14970181
'A characteristic feature of systemic lupus erythematosus is the accumulation of activated/memory T and B cells. These G0/G1-arrested cells express high levels of cyclin-dependent kinase inhibitors such as p21, are resistant to proliferation and apoptosis, and produce large amounts of proinflammatory cytokines. Herein, we show that ablation of p21 in ... More
Mitochondrial permeability transition in the central nervous system: induction by calcium cycling-dependent and -independent pathways.
AuthorsKristal BS, Dubinsky JM
JournalJ Neurochem
PubMed ID9231710
'Isolated rat CNS mitochondria and cultured cortical astrocytes were examined for behavior indicative of a mitochondrial permeability transition (mPT). Exposure of isolated CNS mitochondria to elevated calcium or phosphate or both produced loss of absorbance indicative of mitochondrial swelling. The absorbance decreases were prevented by ADP and Mg2+ and reduced ... More
Characteristics of mitotic cell death induced by enediyne antibiotic lidamycin in human epithelial tumor cells.
AuthorsHe QY, Liang YY, Wang DS, Li DD
JournalInt J Oncol
PubMed ID11788886
'Mitotic cell death, a different cell death mode from apoptosis, has been focused on in tumor therapy. It may involve the mechanism of highly potent cytotoxicities of enediyne antibiotics toward tumor cells. We describe the characteristics of mitotic cell death induced by enediyne antibiotic lidamycin at low concentrations (0.01-1 nM), ... More
Mitochondrial clearance of cytosolic Ca(2+) in stimulated lizard motor nerve terminals proceeds without progressive elevation of mitochondrial matrix [Ca(2+)].
AuthorsDavid G
JournalJ Neurosci
PubMed ID10460256
'This study used fluorescent indicator dyes to measure changes in cytosolic and mitochondrial [Ca(2+)] produced by physiological stimulation of lizard motor nerve terminals. During repetitive action potential discharge at 10-50 Hz, the increase in average cytosolic [Ca(2+)] reached plateau at levels that increased with increasing stimulus frequency. This stabilization of ... More
Mitochondrial mass and membrane potential in coelomocytes from the earthworm Eisenia foetida: studies with fluorescent probes in single intact cells.
AuthorsCossarizza A, Cooper EL, Quaglino D, Salvioli S, Kalachnikova G, Franceschi C
JournalBiochem Biophys Res Commun
PubMed ID7677758
'Earthworm coelomocytes exist in two forms, i.e., small (SC) and large (LC) cells, as demonstrated by velocity sedimentation, electron microscopy, and FCM. However, we know little concerning the functional activities of various, important organelles, such as mitochondria. In comparison with SC, LC from Eisenia foetida have a higher number of ... More
15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress.
AuthorsGarg TK, Chang JY
JournalBMC Pharmacol
PubMed ID15149553
'BACKGROUND: With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H2O2. We also demonstrated that the cytotoxicity caused by H2O2 could be prevented by the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 (15d-PGJ2). RESULTS: Further characterization ... More
Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis.
AuthorsBeltrami E, Plescia J, Wilkinson JC, Duckett CS, Altieri DC
JournalJ Biol Chem
PubMed ID14581472
'Survivin is a member of the Inhibitor of Apoptosis gene family that has been implicated in cell division and suppression of apoptosis. Here, we show that preferential ablation of the nuclear pool of survivin by RNA interference produces a mitotic arrest followed by re-entry into the cell cycle and polyploidy. ... More
(R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage.
AuthorsVoloboueva LA, Liu J, Suh JH, Ames BN, Miller SS
JournalInvest Ophthalmol Vis Sci
PubMed ID16249512
'PURPOSE: To determine whether (R)-alpha-lipoic acid (LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. METHODS: Cultured hfRPE cells were pretreated with various concentrations of LA for 14 to 16 hours followed by treatment with a chemical oxidant, ... More
JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis.
AuthorsSalvioli S, Ardizzoni A, Franceschi C, Cossarizza A
JournalFEBS Lett
PubMed ID9247146
'The sensitivity and specificity of three fluorescent probes used for cytofluorimetric analysis of mitochondrial membrane potential (delta psi) were studied in the U937 human cell line. First, the role of plasmamembrane in influencing the binding of the probes to mitochondria has been investigated. The depolarization of plasmamembrane with high doses ... More
JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia.
AuthorsLegrand O, Perrot JY, Simonin G, Baudard M, Marie JP
JournalBlood
PubMed ID11154229
'One of the best-characterized resistance mechanisms in acute myeloid leukemia (AML) is the drug extrusion mediated by P-glycoprotein (Pgp). Recently the results of workshops organized by several groups concluded that accurate measurement of low activity of Pgp is a difficult goal in clinical samples. Therefore, highly sensitive and specific assays ... More
Bcl-2 protects against FCCP-induced apoptosis and mitochondrial membrane potential depolarization in PC12 cells.
AuthorsDispersyn G, Nuydens R, Connors R, Borgers M, Geerts H
JournalBiochim Biophys Acta
PubMed ID10434055
'This report addresses the relation between Bcl-2 and mitochondrial membrane potential (DeltaPsi(m)) in apoptotic cell death. Rat pheochromocytoma (PC12) cells are differentiated into neuron-like cells with nerve growth factor (NGF). It is known that Bcl-2 can attenuate apoptosis induced by deprivation of neurotrophic factor. The protective effect of Bcl-2 has ... More
Role of oxidant stress in the permeability transition induced in rat hepatic mitochondria by hydrophobic bile acids.
AuthorsSokol RJ, Straka MS, Dahl R, Devereaux MW, Yerushalmi B, Gumpricht E, Elkins N, Everson G
JournalPediatr Res
PubMed ID11264436
'Hydrophobic bile acids may cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. The mechanism for this injury may involve mitochondrial dysfunction and the generation of oxidant stress. The purpose of this study was to determine the relationship of oxidant stress and the mitochondrial membrane permeability transition (MMPT) in hepatocyte ... More
Morphological and functional changes of mitochondria from density separated trout erythrocytes.
AuthorsTiano L, Ballarini P, Santoni G, Wozniak M, Falcioni G
JournalBiochim Biophys Acta
PubMed ID10773157
'Density separated trout erythrocytes, using a discontinuous Percoll gradient, yielded three distinct subfractions (top, middle and bottom) since older cells are characterized by increasing density. Cells from each subfraction were incubated with mitochondria-specific fluorescent probe Mitotracker and JC-1 in order to assess mitochondrial mass and membrane potential by means of ... More
Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics.
AuthorsSarafian TA, Kouyoumjian S, Khoshaghideh F, Tashkin DP, Roth MD
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID12533310
'We have observed rapid and extensive depletion of cellular energy stores by Delta(9)-tetrahydrocannabinol (THC) in the pulmonary transformed cell line A549. ATP levels declined dose dependently with an IC(50) of 7.5 microg/ml of THC after 24-h exposure. Cell death was observed only at concentrations >10 microg/ml. Studies using JC-1, a ... More
Critical upstream signals of cytochrome C release induced by a novel Bcl-2 inhibitor.
AuthorsAn J, Chen Y, Huang Z
JournalJ Biol Chem
PubMed ID14966123
'Cytochrome c release is a central step in the apoptosis induced by many death stimuli. Bcl-2 plays a critical role in controlling this step. In this study, we investigated the upstream mechanism of cytochrome c release induced by ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a recently discovered small molecule inhibitor of Bcl-2. HA14-1 ... More
Calcium is a key signaling molecule in beta-lapachone-mediated cell death.
AuthorsTagliarino C, Pink JJ, Dubyak GR, Nieminen AL, Boothman DA
JournalJ Biol Chem
PubMed ID11279125
'beta-Lapachone (beta-Lap) triggers apoptosis in a number of human breast and prostate cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. Downstream signaling pathway(s) that initiate apoptosis following treatment with beta-Lap have not been elucidated. Since calpain activation was suspected in beta-Lap-mediated apoptosis, ... 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
Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons.
AuthorsHoltsberg FW, Steiner MR, Keller JN, Mark RJ, Mattson MP, Steiner SM
JournalJ Neurochem
PubMed ID9422348
'A diverse body of evidence indicates a role for the lipid biomediator lysophosphatidic acid (LPA) in the CNS. This study identifies and characterizes the induction of neuronal death by LPA. Treatment of cultured hippocampal neurons from embryonic rat brains with 50 microM LPA resulted in neuronal necrosis, as determined morphologically ... More
The K+ channel openers diazoxide and NS1619 induce depolarization of mitochondria and have differential effects on cell Ca2+ in CD34+ cell line KG-1a.
AuthorsKörper S, Nolte F, Rojewski MT, Thiel E, Schrezenmeier H
JournalExp Hematol
PubMed ID12962728
'OBJECTIVE: Mitochondrial membrane potential (deltaPsim) and intracellular Ca2+ play a crucial role in growth and differentiation in hemopoiesis. Some potassium channel openers such as diazoxide have the capacity to elevate cytosolic Ca2+ and depolarize mitochondria in cardiomyocytes. To clarify if such substances have effects on hemopoietic cells we investigated the ... More
High-throughput flow cytometry to detect selective inhibitors of ABCB1, ABCC1, and ABCG2 transporters.
'Up-regulation of pump (transporter) expression and selection of resistant cancer cells result in cancer multidrug resistance to diverse substrates of these transporters. While more than 48 members of the ATP binding cassette (ABC) transporter superfamily have been identified, up to now only three human ABC transporters-ABCB1, ABCC1, and ABCG2-have unambiguously ... More
The membrane potential of the intraerythrocytic malaria parasite Plasmodium falciparum.
AuthorsAllen RJ, Kirk K
JournalJ Biol Chem
PubMed ID14630911
'The membrane potential (Deltapsi) of the mature asexual form of the human malaria parasite, Plasmodium falciparum, isolated from its host erythrocyte using a saponin permeabilization technique, was investigated using both the radiolabeled Deltapsi indicator tetraphenylphosphonium ([(3)H]TPP(+)) and the fluorescent Deltapsi indicator DiBAC(4)(3) (bis-oxonol). For isolated parasites suspended in a high ... More
Neurotoxic nitric oxide rapidly depolarizes and permeabilizes mitochondria by dynamically opening the mitochondrial transition pore.
'Exposure of SH-SY5Y neuroblastoma or rat cortical neurons to diethylenetriamine-NO (DETA-NO) rapidly depolarized mitochondria. In SH-SY5Y DETA-NO activated caspase 3 and produced cell death. Mitochondrial depolarization in SH-SY5Y was visualized both with JC-1 accumulation and as dequenching of calcein fluorescence in mitochondria initially loaded with calcein-AM and tetramethylrhodamine methyl ester ... More
Aeromonas hydrophila cytotoxic enterotoxin activates mitogen-activated protein kinases and induces apoptosis in murine macrophages and human intestinal epithelial cells.
AuthorsGalindo CL, Fadl AA, Sha J, Gutierrez C, Popov VL, Boldogh I, Aggarwal BB, Chopra AK
JournalJ Biol Chem
PubMed ID15215244
'A cytotoxic enterotoxin (Act) of Aeromonas hydrophila possesses several biological activities, induces an inflammatory response in the host, and causes apoptosis of murine macrophages. In this study, we utilized five target cell types (a murine macrophage cell line (RAW 264.7), bone marrow-derived transformed macrophages, murine peritoneal macrophages, and two human ... More
'Huntington disease (HD) is caused by a pathological elongation of CAG repeats in the huntingtin protein gene and is characterized by atrophy and neuronal loss primarily in the striatum. Mitochondrial dysfunction and impaired Ca2+ homeostasis in HD have been suggested previously. Here, we elucidate the effects of Ca2+ on mitochondria ... More
Perturbational profiling of nanomaterial biologic activity.
'Our understanding of the biologic effects (including toxicity) of nanomaterials is incomplete. In vivo animal studies remain the gold standard; however, widespread testing remains impractical, and the development of in vitro assays that correlate with in vivo activity has proven challenging. Here, we demonstrate the feasibility of analyzing in vitro ... More
The effects of ethidium bromide induced loss of mitochondrial DNA on mitochondrial phenotype and ultrastructure in a human leukemia T-cell line (MOLT-4 cells).
AuthorsArmand R, Channon JY, Kintner J, White KA, Miselis KA, Perez RP, Lewis LD
JournalToxicol Appl Pharmacol
PubMed ID15050409
'Mitochondrial DNA-deficient (rho(0)) cells were generated following a 26-day incubation of MOLT-4 lymphoblastoid T cells in ethidium bromide (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide). The absence of mitochondrial DNA (mtDNA) in the resultant MOLT-4 rho(0) cells was confirmed by Southern analysis and quantitative polymerase chain reaction (PCR). MOLT-4 rho(0) cells proliferated more slowly than ... More
Mmd1p, a novel, conserved protein essential for normal mitochondrial morphology and distribution in the fission yeast Schizosaccharomyces pombe.
AuthorsWeir BA, Yaffe MP
JournalMol Biol Cell
PubMed ID14767070
'The mmd1 mutation causes temperature-sensitive growth and defects in mitochondrial morphology and distribution in the fission yeast Schizosaccharomyces pombe. In mutant cells, mitochondria aggregate at the two cell ends, with increased aggregation at elevated temperatures. Microtubules, which mediate mitochondrial positioning in fission yeast, seem normal in mmd1 cells at permissive ... 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
Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis.
AuthorsBortner CD, Sifre MI, Cidlowski JA,
JournalJ Biol Chem
PubMed ID18187415
'Cell shrinkage, or apoptotic volume decrease (AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that ... More
Dehydroepiandrosterone with other neurosteroids preserve neuronal mitochondria from calcium overload.
AuthorsKaasik A, Safiulina D, Kalda A, Zharkovsky A
JournalJ Steroid Biochem Mol Biol
PubMed ID14630095
'This current study was designed to test whether the dehydroepiandrosterone (DHEA) and other neurosteroids could improve mitochondrial resistance to ischemic damage and cytoplasmic Ca(2+) overload. To imitate these mechanisms at mitochondrial level we treated the saponin permeabilized neurons either with the respiratory chain inhibitor, 1-methyl-4-phenylpyridinium or raised free extra-mitochondrial [Ca(2+)]. ... More
P-glycoprotein inhibitors modulate accumulation and efflux of xenobiotics in extra and intracellular Toxoplasma gondii.
AuthorsSauvage V, Aubert D, Bonhomme A, Pinon JM, Millot JM
JournalMol Biochem Parasitol
PubMed ID14747146
'We examined xenobiotic transport and the effects of P-glycoprotein (Pgp) inhibitors on efflux function in Toxoplasma gondii tachyzoites. The fluorescence emission of JC-1 and daunorubicin (Pgp substrates) was determined in both extracellular tachyzoites and T. gondii-infected human KB cells. Dye accumulation and efflux were modulated by verapamil (Vp) and cyclosporin ... More
Tyrphostins protect neuronal cells from oxidative stress.
AuthorsSagara Y, Ishige K, Tsai C, Maher P,
JournalJ Biol Chem
PubMed ID12121989
'Tyrphostins are a family of tyrosine kinase inhibitors originally synthesized as potential anticarcinogenic compounds. Because tyrphostins have chemical structures similar to those of the phenolic antioxidants, we decided to test the protective efficacy of tyrphostins against oxidative stress-induced nerve cell death (oxytosis). Many commercially available tyrphostins, at concentrations ranging from ... 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