共查询到20条相似文献,搜索用时 31 毫秒
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Cabreiro F Picot CR Perichon M Castel J Friguet B Petropoulos I 《The Journal of biological chemistry》2008,283(24):16673-16681
According to the mitochondrial theory of aging, mitochondrial dysfunction increases intracellular reactive oxidative species production, leading to the oxidation of macromolecules and ultimately to cell death. In this study, we investigated the role of the mitochondrial methionine sulfoxide reductase B2 in the protection against oxidative stress. We report, for the first time, that overexpression of methionine sulfoxide reductase B2 in mitochondria of acute T-lymphoblastic leukemia MOLT-4 cell line, in which methionine sulfoxide reductase A is missing, markedly protects against hydrogen peroxide-induced oxidative stress by scavenging reactive oxygen species. The addition of hydrogen peroxide provoked a time-gradual increase of intracellular reactive oxygen species, leading to a loss in mitochondrial membrane potential and to protein carbonyl accumulation, whereas in methionine sulfoxide reductase B2-overexpressing cells, intracellular reactive oxygen species and protein oxidation remained low with the mitochondrial membrane potential highly maintained. Moreover, in these cells, delayed apoptosis was shown by a decrease in the cleavage of the apoptotic marker poly(ADP-ribose) polymerase-1 and by the lower percentage of Annexin-V-positive cells in the late and early apoptotic stages. We also provide evidence for the protective mechanism of methionine sulfoxide reductase B2 against protein oxidative damages. Our results emphasize that upon oxidative stress, the overexpression of methionine sulfoxide reductase B2 leads to the preservation of mitochondrial integrity by decreasing the intracellular reactive oxygen species build-up through its scavenging role, hence contributing to cell survival and protein maintenance. 相似文献
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Involvement of mitochondrial phospholipid hydroperoxide glutathione peroxidase as an antiapoptotic factor 总被引:1,自引:0,他引:1
Although reactive oxygen species (ROS) such as superoxide and hydroperoxide are known to induce apoptotic cell death, little is known as to the apoptotic death signaling of mitochondrial ROS. Recent evidence has suggested that antioxidant enzymes in mitochondria may be responsible for the regulation of cytochrome c release and apoptotic cell death. This paper examines the current state of knowledge regarding the role of mitochondrial antioxidant enzymes, especially phospholipid hydroperoxide glutathione peroxidase. A model for the release of cytochrome c by lipid hydroperoxide has also been proposed. 相似文献
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Ultraviolet B (UVB medium wave, 280–315 nm) induces cellular oxidative damage and apoptosis by producing reactive oxygen species (ROS). Glutathione peroxidase functions as an antioxidant by catalyzing the reduction of hydrogen peroxide, the more important member of reactive oxygen species. A human selenium-containing single-chain variable fragment (se-scFv-B3) with glutathione peroxidase activity of 1288 U/μmol was generated and investigated for its antioxidant effects in UVB-induced oxidative damage model. In particular, cell viability, lipid peroxidation extent, cell apoptosis, the change of mitochondrial membrane potential, caspase-3 activity and the levels of intracellular reactive oxygen species were assayed. Human se-scFv-B3 protects NIH3T3 cells against ultraviolet B-induced oxidative damage and subsequent apoptosis by prevention of lipid peroxidation, inhibition of the collapse of mitochondrial membrane potential as well as the suppression of the caspase-3 activity and the level of intracellular ROS. It seems that antioxidant effects of human se-scFv-B3 are mainly associated with its capability to scavenge reactive oxygen species, which is similar to that of the natural glutathione peroxidase. 相似文献
5.
Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. We investigated the effects of the manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of gamma-irradiation, there was a distinct difference between the control cells and the cells pre-treated with 5 microM MnTMPyP for 2 h with regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH+GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP(+)+NADPH] ratio was lower in control cells compared to MnTMPyP-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production were significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl-2 compared to control cells upon exposure to ionizing radiation. This study indicates that MnTMPyP may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species. 相似文献
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Kuznetsov AV Smigelskaite J Doblander C Janakiraman M Hermann M Wurm M Scheidl SF Sucher R Deutschmann A Troppmair J 《Molecular and cellular biology》2008,28(7):2304-2313
Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca(2+). Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca(2+) levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca(2+), which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca(2+) overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca(2+) homeostasis. 相似文献
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Barros MH Bandy B Tahara EB Kowaltowski AJ 《The Journal of biological chemistry》2004,279(48):49883-49888
Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span. 相似文献
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Cámara Y Duval C Sibille B Villarroya F 《The international journal of biochemistry & cell biology》2007,39(1):146-160
While the acquisition of apoptosis resistance is part of the differentiation program of skeletal muscle cells, differentiated muscle cells can undergo apoptosis in response to physiological or pathological stimuli. The generation of reactive oxygen species by mitochondria plays a major role in the control of apoptosis in many cell types. Indeed their involvement in controlling apoptosis in differentiated muscle cells, or in generating resistance to apoptosis remains unknown. Moreover, differentiated muscle cells specifically express the uncoupling protein-3, a mitochondrial protein potentially involved in controlling reactive oxygen species production. To study the role of mitochondrial reactive oxygen species in the control of apoptosis in skeletal muscle cells, L6E9 myoblasts and myotubes were exposed to staurosporine, an inducer of apoptosis via mitochondrial pathways. Staurosporine activated apoptotic pathways (i.e. caspase-3 and caspase-9) increasing reactive oxygen species in myoblasts and, to a minor extent, in myotubes. However, the increase in reactive oxygen species was not needed to induce apoptosis nor was it involved in the differential sensitization of myoblasts and myotubes to apoptosis. Moreover, expression of uncoupling protein-3 in myotubes did not affect reactive oxygen species production, although it produced a slight sensitization for staurosporine-induced apoptosis. Results indicate that apoptotic activation in skeletal muscle cells mainly involves reactive oxygen species-independent mechanisms and that mitochondrial uncoupling protein-3 is not protective either for reactive oxygen species production or for apoptotic activation in muscle cells. 相似文献
10.
Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture 总被引:7,自引:0,他引:7
López E Arce C Oset-Gasque MJ Cañadas S González MP 《Free radical biology & medicine》2006,40(6):940-951
Cadmium is a toxic agent that it is also an environmental contaminant. Cadmium exposure may be implicated in some humans disorders related to hyperactivity and increased aggressiveness. This study presents data indicating that cadmium induces cellular death in cortical neurons in culture. This death could be mediated by an apoptotic and a necrotic mechanism. The apoptotic death may be mediated by oxidative stress with reactive oxygen species (ROS) formation which could be induced by mitochondrial membrane dysfunction since this cation produces: (a) depletion of mitochondrial membrane potential and (b) diminution of ATP levels with ATP release. Necrotic death could be mediated by lipid peroxidation induced by cadmium through an indirect mechanism (ROS formation). On the other hand, 40% of the cells survive cadmium action. This survival seems to be mediated by the ability of these cells to activate antioxidant defense systems, since cadmium reduced the intracellular glutathione levels and induced catalase and SOD activation in these cells. 相似文献
11.
Kim HJ Shin SW Oh CJ Lee MH Yang CH Park JW 《Redox report : communications in free radical research》2005,10(6):287-293
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Therefore, compounds that scavenge reactive oxygen species may regulate heat shock-induced cell death. Recently, it has been shown that the decomposition product of the spin-trapping agent alpha-phenyl-N-t-butylnitrone, N-t-butyl hydroxylamine (NtBHA), mimics alpha-phenyl-N-t-butylnitrone and is much more potent in delaying reactive oxygen species-associated senescence. We investigated the protective role of NtBHA against heat shock-induced apoptosis in U937 cells. Upon exposure to heat shock, there was a distinct difference between the untreated cells and the cells pre-treated with 0.1 mM NtBHA for 2 h in regard to apoptotic parameters, cellular redox status, and mitochondrial function. Upon exposure to heat shock, NtBHA pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax, and down-regulation of Bcl-2 compared to untreated cells. This study indicates that NtBHA may play an important role in regulating the apoptosis induced by heat shock, presumably through scavenging of reactive oxygen species. 相似文献
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Within the central nervous system and under normal conditions, nitric oxide (NO) is an important physiological signaling molecule. When produced in large excess, NO also displays neurotoxicity. In our previous report, we have demonstrated that the exposure of neuronal cells to NO donors induced apoptotic cell death, while pretreatment with free radical scavengers L-ascorbic acid 2-[3, 4-dihydro-2,5,7,8-tetramethyl-2-(4,8, 12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1) or superoxide dismutase attenuated apoptosis effectively, suggesting that reactive oxygen species (ROS) may be involved in the cascade of events leading to apoptosis. In the present investigation, we directly studied the kinetic generation of ROS in NO-treated neuronal cells by flow cytometry using 2', 7'-dichloro-fluorescein diacetate and dihydrorhodamine 123 as redox-sensitive fluorescence probes. The results indicated that exposure of cerebellar granule cells to the NO donor S-nitroso-N-acetylpenicillamine (SNAP) induced oxidative stress, which was characterized by the accumulation of cytosolic and mitochondrial ROS, the increase in the extracellular hydrogen peroxide level, and the formation of lipid peroxidation products. SNAP treatment also induced apoptotic cell death as confirmed by the formation of cytosolic mono- and oligonucleosomes. Pretreating cells with the novel antioxidant EPC-K1 effectively prevented oxidative stress induced by SNAP, and attenuated cells from apoptosis. 相似文献
13.
Storz P 《Trends in cell biology》2007,17(1):13-18
The mitochondrial electron transport chain is the major source for the production of oxygen radicals. Mitochondria-generated reactive oxygen species (mROS) have been implicated in decreasing the life span and contributing to age-related diseases (known as the free radical theory of aging). Recently, the serine/threonine kinase protein kinase D1 (PKD1) was identified as a mitochondrial sensor for oxidative stress. mROS-activated PKD regulates a radical-sensing signaling pathway, which relays mROS production to the induction of nuclear genes that mediate cellular detoxification and survival. This PKD regulated signaling pathway is the first known mitochondria located and mitochondrially regulated antioxidant system that protects these organelles and cells from oxidative stress-mediated damage or cell death. The identification of this and further intracellular protective signaling pathways provides an opportunity to manipulate the effects of mROS, and might provide the key to targeting aging effects and age-related diseases that have been linked to mitochondrial dysfunctions. 相似文献
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Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells 总被引:3,自引:0,他引:3
Cheng X Shimizu I Yuan Y Wei M Shen M Huang H Urata M Sannomiya K Fukuno H Hashimoto-Tamaoki T Ito S 《Life sciences》2006,79(21):1988-1994
Oxidative stress, including the generation of reactive oxygen species (ROS), is known to be involved in apoptosis. Preventing apoptosis may thereby induce a malignant transformation of liver tumor cells. Estradiol (E2) is a potent endogenous antioxidant. We examined the proapoptotic role of progesterone as well as the antiapoptotic role of E2 in human hepatoma HuH-7 cells in a state of early apoptosis induced by tumor necrosis factor (TNF) alpha. The TNF alpha-induced ROS generation, lipid peroxidation, antioxidant enzyme consumption, a proapoptotic predominant expression of Bcl-2 family proteins, and a disruption of mitochondrial membrane potential were all inhibited by E2, and then they were further stimulated by progesterone in HuH-7 cells. The inhibitory effects of E2 were blocked by coincubation with progesterone. Treatment with the progesterone receptor antagonist RU486 led to the blockage of the progesterone-mediated responses to E2 pretreatment in TNF alpha-induced apoptosis. These findings demonstrate that E2 inhibits the TNF alpha-induced early apoptosis in hepatoma cells, by suppressing the oxidative stress processes, whereas progesterone acts in a manner opposite from the effects of E2, and the inhibitory effects of E2 were blocked by progesterone, thus leading to the apoptosis of hepatoma cells. 相似文献
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Severi T Vander Borght S Libbrecht L VanAelst L Nevens F Roskams T Cassiman D Fevery J Verslype C van Pelt JF 《Chemico-biological interactions》2007,168(2):128-134
Hepatitis virus replication in the liver is often accompanied by inflammation resulting in the formation of reactive oxygen species (ROS) and nitric oxide (NO) and these may induce cell death. We investigated whether the expression of HBx or HCV core protein in HepG2 cells has an influence on the sensitivity of these cells for oxidative radicals. Our previous study, using the inducible HBV model of HepAD38, revealed that oxidative-stress-related genes are upregulated by virus replication. In the present study, we examined the intracellular pro-oxidant status with dichlorofluorescein (DCF) in HepG2 cell lines transfected with HBx, HbsAg and HCV core. Baseline intracellular oxidative levels were not different in the cell lines expressing viral proteins as compared to control. However, when these cells were exposed to H(2)O(2), the viral protein expressing cells, especially those expressing HBx, showed a reduced level of ROS. This suggests that HBx and HCV core transfected cells can convert H(2)O(2) to less reactive compounds at a higher rate than the control cells. When HBx or HCV core expressing cells were exposed to peroxynitrite (a highly reactive product formed under physiological conditions through interaction of superoxide (O(2)(-)) with NO) these cells were less sensitive to induction of cell death. In addition, these cell lines were less prone to cell death when exposed to H(2)O(2) directly. In conclusion, HBx and HCV core expression in HepG2 cells leads to a survival benefit under oxidative stress which in vivo can be induced during inflammation. 相似文献
16.
Pajusto M Toivonen TH Tarkkanen J Jokitalo E Mattila PS 《Apoptosis : an international journal on programmed cell death》2005,10(6):1433-1443
Reactive oxygen species are toxic to cells but they may also have active roles in transducing apoptotic events. To study the
role of reactive oxygen species in growth factor depletion induced apoptosis of human primary CD4+ T cells, we used a synthetic
manganese porphyrin superoxide dismutase mimetic to detoxify superoxide anions formed during apoptosis. Apoptosis of primary
CD4+ T cells was characterized by generation of superoxide anions, plasma membrane phosphatidyl-serine translocation, loss
of mitochondrial membrane potential, activation of caspase 3, condensation of chromatin, as well as DNA degradation. The detoxification
of superoxide anions did not influence plasma membrane phosphatidyl-serine translocation, or chromatin condensation, and only
marginally inhibited the loss of mitochondrial membrane potential and the formation of DNA strand breaks. In contrast, the
detoxification of superoxide anions significantly reduced caspase 3 activity and almost completely inhibited the apoptotic
decrease in total cellular DNA content as measured by propidium iodide staining. Our results indicate that reactive oxygen
anions induce signals leading to efficient DNA degradation after the initial formation of DNA strand breaks. Thus, reactive
oxygen anions have active roles in signaling that lead to the apoptotic events. 相似文献
17.
Jun-Feng Chen Hong Liu Hai-Feng Ni Lin-Li Lv Ming-Hui Zhang Ai-Hua Zhang Ri-Ning Tang Ping-Sheng Chen Bi-Cheng Liu 《PloS one》2013,8(12)
Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells. 相似文献
18.
Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis 总被引:2,自引:0,他引:2
Tamm C Zhivotovsky B Ceccatelli S 《Apoptosis : an international journal on programmed cell death》2008,13(3):354-363
Oxidative stress occurs as a consequence of disturbance in the balance between the generation of reactive oxygen species (ROS)
and the antioxidant defence mechanisms. The interaction of ROS with DNA can cause single-, or double-strand breaks that subsequently
can lead to the activation of p53, which is central for the regulation of cellular response, e.g. apoptosis, to a range of
environmental and intracellular stresses. Previous reports have suggested a regulatory role of p53 in the early activation
of caspase-2, upstream of mitochondrial apoptotic signaling. Here we show that excessive ROS formation, induced by 2,3-dimethoxy-1,4-naphthoquinone
(DMNQ) exposure, induces apoptosis in primary cultured neural stem cells (NSCs) from cortices of E15 rat embryos. Following
DMNQ exposure cells exhibited apoptotic hallmarks such as Bax oligomerization and activation, cytochrome c release, caspase activation and chromatin condensation. Additionally, we could show early p53 accumulation and a subsequent
activation of caspase-2. The attenuation of caspase-2 activity with selective inhibitors could antagonize the mitochondrial
signaling pathway and cell death. Overall, our results strongly suggest that DMNQ-induced oxidative stress causes p53 accumulation
and consequently caspase-2 activation, which in turn initiates apoptotic cell death via the mitochondria-mediated caspase-dependent
pathway in NSCs. 相似文献
19.
Mitochondrial oxidative burst involved in apoptotic response in oats 总被引:10,自引:0,他引:10
Yao N Tada Y Sakamoto M Nakayashiki H Park P Tosa Y Mayama S 《The Plant journal : for cell and molecular biology》2002,30(5):567-579
Apoptotic cell response in oats is induced by victorin, a host-selective toxin secreted by Cochliobolus victoriae and thought to exert toxicity by inhibiting mitochondrial glycine decarboxylase (GDC) in Pc-2/Vb oats. We examined the role of mitochondria, especially the organelle-derived production of reactive oxygen species (ROS), in the induction of apoptotic cell death. Cytofluorimetric analysis showed that victorin caused mitochondrial deltaPsim breakdown and mitochondrial oxidative burst. Ultrastructural analysis using a cytochemical assay based on the reaction of H2O2 with CeCl3 detected H2O2 eruption at permeability transition pore-like sites on the mitochondrial membrane in oat cells treated with victorin. ROS generation preceded the apoptotic cell responses seen in chromatin condensation and DNA laddering. Both aminoacetonitrile (a specific GDC inhibitor) and antimycin A (a mitochondrial complex III inhibitor) also induced mitochondrial H2O2 eruption, and led to the apoptotic response in oat cells. ROS scavengers such as N-acetyl-l-cysteine and catalase suppressed the mitochondrial oxidative burst and delayed chromatin condensation and DNA laddering in the victorin- or antimycin A-treated leaves. These findings indicate possible involvement of mitochondria, especially mitochondrial-derived ROS generation, as an important regulator in controlling apoptotic cell death in oats. 相似文献
20.
Ji-Hua Ren Xiang Chen Li Zhou Na-Na Tao Hong-Zhong Zhou Bo Liu Wan-Yu Li Ai-Long Huang Juan Chen 《PloS one》2016,11(3)