Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on evidence that oxidative stress during apoptosis is controlled, at least in part, by modulating cellular antioxidant defences. Evidence is presented from studies of apoptosis induced by glucocorticoids, HIV-1 infection and tumour necrosis factor-alpha. Glucocorticoid treatment of murine lymphocyte cell lines leads to the down-regulation of primary antioxidant defence enzymes, including catalase, superoxide dismutases, thioredoxin and DT-diaphorase. Following HIV-1 infection, disturbances in glutathione metabolism are seen, and decreased antioxidant enzyme activities have been reported for HIV-1-infected cell lines. The viral protein Tat may mediate these effects. Cellular resistance to apoptosis induced by tumour necrosis factor-alpha is modulated by the expression of manganese superoxide dismutase or Bcl-2. The loss of antioxidant defences is predicted to lead to oxidative stress, which could contribute to the mechanism of apoptosis through an effect on redox-sensitive transcription factors, calcium homeostasis or cysteine proteases.
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PMID:Modulation of the antioxidant defence as a factor in apoptosis. 1718 56

While acute oxidative stress triggers cell apoptosis or necrosis, persistent oxidative stress induces genomic instability and has been implicated in tumor progression and drug resistance. In a previous report, we demonstrated that reactive oxygen species modulator 1 (Romo1) expression was up-regulated in most cancer cell lines and suggested that increased Romo1 expression might confer chronic oxidative stress to tumor cells. In this study, we show that enforced Romo1 expression induces reactive oxygen species (ROS) production in the mitochondria leading to massive cell death. However, tumor cells that adapt to oxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, and Bcl-2 showed drug resistance to 5-FU. To elucidate the relationship between 5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit 5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked 5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROS production through Romo1 induction. Based on these results we suggest that cellular adaptive response to Romo1-induced ROS is another mechanism of drug resistance to 5-FU and Romo1 expression may provide a new clinical implication in drug resistance of cancer chemotherapy.
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PMID:Drug resistance to 5-FU linked to reactive oxygen species modulator 1. 1753 4

Mitochondrial myopathy patients (MMPs) have impaired oxidative phosphorylation and exercise intolerance. Endurance training of MMPs improves exercise tolerance, but also increases mutational load. To assess the regulation of mitochondrial content in MMPs, we measured proteins involved in 1) biogenesis, 2) oxidative stress, and 3) apoptosis in MMPs and healthy controls (HCs) both before and after endurance training. Before training, MMPs had a greater mitochondrial content, along with a 1.4-fold (P < 0.05) higher expression of the biogenesis regulator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). The DNA repair enzyme 8-oxoguanine DNA glycolase-1 (OGG-1), the antioxidant manganese superoxide dismutase (MnSOD), and the apoptotic proteins AIF and Bcl-2 were higher in MMPs compared with HCs. Aconitase, an enzyme sensitive to oxidative stress, was 52% lower (P < 0.05) in MMPs when calculated based on an estimate of mitochondrial volume and oxidative stress-induced protein modifications tended to be higher in MMPs compared with HCs. Endurance training (ET) induced increases in mitochondrial content in both HC subjects and MMPs, but there was no effect of training on the regulatory proteins Tfam or PGC-1alpha. In MMPs, training induced a selective reduction of OGG-1, an increase in MnSOD, and a reduction in aconitase activity. Thus, before training, MMPs exhibited an adaptive response of nuclear proteins indicative of a compensatory increase in mitochondrial content. Following training, several parallel adaptations occurred in MMPs and HCs, which may contribute to previously observed functional improvements of exercise in MMPs. However, our results indicate that muscle from MMPs may be exposed to greater levels of oxidative stress during the course of training. Further investigation is required to evaluate the long-term benefits of endurance training as a therapeutic intervention for mitochondrial myopathy patients.
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PMID:The effect of training on the expression of mitochondrial biogenesis- and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects. 1755 Oct 3

Adriamycin is an effective anthracycline anti-tumor antibiotic. However, the clinical use of adriamycin has been restricted by its serious side effects. Some reports indicated that the side effects of adriamycin could cause systemic injury, in which reactive oxygen species (ROS) play an important role. ROS are a large family of oxygen free radical and non-free radical active oxygen-containing molecules, including superoxide radical, hydrogen peroxide and hydroxyl radical, which contribute to oxidative stress. Although antioxidant treatment is a promising method to prevent the side effects, protection by a single antioxidant is limited. The Chinese herbal medicine ANTIOXIN is a multiple antioxidant that can effectively block oxidative stress. It was hypothesized that ANTIOXIN could effectively reduce the side effects of adriamycin. A rat tumor model with a transplanted tumor in the liver was treated with adriamycin and ANTIOXIN was used as a protection. Oxidative stress and antioxidant enzymes were evaluated. The results showed that adriamycin chemotherapy increased the level of malondialdehyde (MDA), nitrogen oxide (NO) and decreased the activities of total superoxide dismutase (T-SOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAC). Adriamycin chemotherapy also decreased the expression of Bcl-2, increased the expression of iNOS and cell apoptosis in the liver and kidney. Multiple antioxidants ANTIOXIN had an antagonistic effect on these changes and significantly decreased the mortality of the experimental rats. These data demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of 'multiple antioxidant chain' had effective protection.
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PMID:Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy. 1758 87

Malignant gliomas are resistant to various proapoptotic therapies, such as radiotherapy and conventional chemotherapy. In this study, we show that selenite is preferentially cytotoxic to various human glioma cells over normal astrocytes via autophagic cell death. Overexpression of Akt, survivin, XIAP, Bcl-2, or Bcl-xL failed to block selenite-induced cell death, suggesting that selenite treatment may offer a potential therapeutic strategy against malignant gliomas with apoptotic defects. Before selenite-induced cell death in glioma cells, disruption of the mitochondrial cristae, loss of mitochondrial membrane potential, and subsequent entrapment of disorganized mitochondria within autophagosomes or autophagolysosomes along with degradation of mitochondrial proteins were noted, showing that selenite induces autophagy in which mitochondria serve as the main target. At the early phase of selenite treatment, high levels of superoxide anion were generated and overexpression of copper/zinc superoxide dismutase or manganese superoxide dismutase, but not catalase, significantly blocked selenite-induced mitochondrial damage and subsequent autophagic cell death. Furthermore, treatment with diquat, a superoxide generator, induced autophagic cell death in glioma cells. Taken together, our study clearly shows that superoxide anion generated by selenite triggers mitochondrial damage and subsequent mitophagy, leading to irreversible cell death in glioma cells.
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PMID:Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells. 1761 90

Thyroid hormone (TH; 3,3',5-triiodothyronine, T3) is required for the normal function of most tissues, with major effects on O(2) consumption and metabolic rate. These are due to transcriptional activation of respiratory genes through the interaction of T3-liganded TH receptors with TH response elements or the activation of intermediate factors, with the consequent higher production of reactive O(2) species (ROS) and antioxidant depletion. T3-induced oxidative stress in the liver triggers the redox upregulation of the expression of cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-10), enzymes (inducible nitric oxide synthase, manganese superoxide dismutase), and anti-apoptotic proteins (Bcl-2), via a cascade initiated by TNF-alpha produced by Kupffer cells, involving inhibitor of kappaB phosphorylation and nuclear factor-kappaB activation. Thus, TH calorigenesis triggers an expression pattern that may represent an adaptive mechanism to re-establish redox homeostasis and promote cell survival under conditions of ROS toxicity secondary to TH-induced oxidative stress. Mechanisms of expression of respiratory and redox-sensitive genes may be functionally integrated, which could be of importance to understand the complexities of TH action and the outcome of thyroid gland dysfunction.
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PMID:The role of thyroid hormone calorigenesis in the redox regulation of gene expression. 1765 42

Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.
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PMID:Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain. 1956 Apr 81

The present study examined the effects of KIOM-79 on streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic beta-cells (RINm5F). KIOM-79 is a mixture of plant extracts from parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix. A marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ induced diabetic cells, which returned to control conditions after KIOM-79 treatment. Mitochondrial manganese superoxide dismutase (Mn SOD) activity and its protein expression were downregulated by STZ treatment but upregulated by KIOM-79 treatment. In addition, KIOM-79 treatment restored the loss of the mitochondrial membrane potential (Deltapsi) produced by STZ treatment. KIOM-79 induced an increase in Bcl-2 and a decrease in phospho Bcl-2 and Bax, which are related to permeability of the mitochondrial membrane. Further, KIOM-79 inhibited the translocation of cytochrome c from the mitochondria to the cytosol and elevated the ATP level, which was reduced by STZ treatment. These results suggest that KIOM-79 exhibits a protective effect through activation of antioxidant defense mechanisms and by attenuation of mitochondrial dysfunction in STZ-induced diabetic cells.
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PMID:Effect of KIOM-79 against mitochondrial damage induced by streptozotocin in pancreatic beta-cells. 2007 88

Oxidative stress-induced mitochondrial dysfunction is a common consequence of severe sepsis. However, oxidative stress also activates signalling cascades which enable protection of cells against subsequent oxidative damage. This study hypothesized that cellular uptake of vitamin C as dehydroascorbic acid rather than ascorbic acid would up-regulate antioxidant enzyme systems and impart a protective effect to mitochondria in cells subsequently exposed to lipopolysaccharide (LPS) in an iron free environment. Treatment of monocytes with dehydroascorbic acid, but not ascorbic acid, caused oxidative stress (p< 0.001). Dehydroascorbic acid exposure also resulted in increased manganese superoxide dismutase (p= 0.018) and catalase (p= 0.003) expression. Pre-treatment of monocytes with dehydroascorbic acid followed by LPS resulted in higher mitochondrial membrane potentials than cells without pre-treatment (p< 0.0001). Lower cytochrome c in cytosol (p< 0.05) and higher mitochondrial expression of the anti-apoptotic Bcl-2 protein (p= 0.029) was also found in monocytes pre-treated before subsequent LPS exposure, compared to cells without pre-treatment. In conclusion, acute exposure of monocytes to dehydroascorbic acid in an iron free environment induces cytoprotective antioxidant enzymes and protected mitochondria from the harmful effects of oxidative stress prior to a septic insult, which was abrogated when cells were pre-incubated with the DHA uptake inhibitor cytocholasin B.
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PMID:Dehydroascorbic acid as pre-conditioner: protection from lipopolysaccharide induced mitochondrial damage. 2016 93

It is now well established that oxidative stress plays a causative role in the pathogenesis of anoxia/reoxygenation (A/R) injury. Ganoderma atrum polysaccharide (PSG-1), the most abundant component isolated from G. atrum, has been shown to possess potent antioxidant activity. The goals of this study were to investigate the effect of PSG-1 against oxidative stress induced by A/R injury and the possible mechanisms in cardiomyocytes. In this work, primary cultures of neonatal rat cardiomyocytes pretreated with PSG-1 were subjected to A/R and subsequently monitored for cell viability by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The levels of intracellular reactive oxygen species (ROS), apoptosis, and mitochondrial membrane potential (Deltapsi(m)) were determined by flow cytometry. Western blot analysis was used to measure the expression of cytochrome c, Bcl-2 family, and manganese superoxide dismutase (MnSOD) proteins, and the activities of caspase-3 and caspase-9 were determined by a colorimetric method. The results showed that PSG-1 protected against cell death caused by A/R injury in cardiomyocytes. PSG-1 reduced the A/R-induced ROS generation, the loss of mitochondrial membrane potential (Deltapsi(m)), and the release of cytochrome c from the mitochondria into cytosol. PSG-1 inhibited the A/R-stimulated activation of caspase-9 and caspase-3 and alteration of Bcl-2 family proteins. Moreover, PSG-1 significantly increased the protein expression of MnSOD in cardiomyocytes. These findings suggest that PSG-1 significantly attenuates A/R-induced oxidative stress and improves cell survival in cardiomyocytes through mitochondrial pathway.
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PMID:Ganoderma atrum polysaccharide protects cardiomyocytes against anoxia/reoxygenation-induced oxidative stress by mitochondrial pathway. 2021 39


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