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)

Mitochondrial membrane potential is reduced in copper-deficient rat hearts, but it is uncertain if this will lead to the onset of apoptosis. To determine if copper deficiency per se leads to apoptosis, C2C12 cells were made copper deficient by treatment with the copper chelator tetraethylenepentamine (TEPA). In TEPA-treated cells, the activity of Cu, Zn-superoxide dismutase and cytochrome-c oxidase decreased dramatically. The protein levels of nuclear-encoded subunits of the cytochromie-c oxidase decreased, but the mitochondrial-encoded subunits remained unchanged. Decreased mitochondrial membrane potential was indicated in TEPA-treated cells, but further investigation of the potential induction of apoptosis by measuring caspase-3 activity, protein concentrations of Bcl-2 and Bax, and DNA fragmentation suggested that apoptosis is not induced in TEPA-treated C2C12 cells. Cells with decreased mitochondrial membrane potential were not destined to apoptosis as a result of copper deficiency.
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PMID:Mitochondrial membrane potential is reduced in copper-deficient C2C12 cells in the absence of apoptosis. 1603 10

Aging-related changes of tubular cell apoptosis and its mechanisms in renal ischemia/reperfusion (I/R) injury are unclear. In the present study, aged (27-month-old) and young (3-month-old) Wistar rats were used to investigate aging-related tubular cell apoptosis in the setting of renal I/R injury. The renal I/R model was induced by clamping bilateral renal arteries for 30 minutes followed by reperfusion for 18 hours. Cyclosporine A (CsA, 2 mg/kg) or mycophenolate mofetil (MMF, 20 mg/kg/d) was used before ischemia. Age-matched sham-operated rats served as controls. We found that tubular cell apoptosis increased more significantly in aged rats than in young rats after renal I/R. More pronounced increases of Bax/Bcl-2 ratio, cytosolic cytochrome c, and caspase-9, which are involved in mitochondria-mediated apoptosis, were found in aged rats than in young rats, and were associated with a more pronounced decrease in superoxide dismutase activity and increase of malondialdehyde content. However, increases of tumor necrosis factor-alpha and caspase-8, two components of death receptor-mediated apoptosis, showed no aging-related differences. Interfering mitochondria and death receptor pathways with CsA and MMF, respectively, reduced the apoptosis in both age groups, whereas CsA was more effective in aged rats. Our results have demonstrated that there was an aging-related increase of tubular cell apoptosis in the renal I/R model, which may be, at least partly, due to an enhanced mitochondrial pathway resulting possibly from increased oxidative stress.
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PMID:Mitochondrial pathway is responsible for aging-related increase of tubular cell apoptosis in renal ischemia/reperfusion injury. 1607 4

Rosmarinic acid (RA) is a naturally occurring polyphenolic and is found in several herbs in the Lamiaceae family, such as, Perilla frutescens. ADR is a potent anti-tumor drug, but is unfortunately potently cardiotoxic. This study was undertaken to investigate the inhibitory effect of RA on ADR-induced apoptosis in H9c2 cardiac muscle cells at a mechanistic level. In vitro, ADR significantly decreased the viabilities of H9c2 cells, and this was accompanied by apoptotic features, such as a change in nuclear morphology and caspase protease activation. RA was found to markedly inhibit these apoptotic characteristics by reducing intracellular ROS generation and by recovering the mitochondria membrane potential (delta psi). In addition, RA reversed the downregulations of GSH, SOD and Bcl-2 by ADR. In the present study, ADR was found to activate c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), transcriptional factor-activator-protein (AP)-1. We found that c-fos, Jun-B, Jun-D and p-c-Jun were super shifted by ADR, indicating that these proteins have an important role in the ADR-induced AP-1 activation. The inhibitions of JNK and ERK using appropriate inhibitors or dominant negative cell lines reduced ADR-induced apoptosis in H9c2 cardiac muscle cells. Taken together, these results suggest that RA can inhibit ADR-induced apoptosis in H9C2 cardiac muscle cells by inhibiting ROS generation and JNK and ERK activation. Thus, we propose that RA should be viewed as a potential chemotherapeutic that inhibits cardiotoxicity in ADR-exposed patients.
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PMID:Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2 cardiac muscle cells by inhibiting reactive oxygen species and the activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase. 1610 32

Combined radiotherapy and chemotherapy have represented major advance in the therapeutic management of cancer therapy. Anthracycline antineoplastic agents are limited by a high incidence of severe and usually irreversible cardiac toxicity, the cause of which remains controversial. When the primary cardiomyocytes isolated from neonatal rats were preirradiated by gamma-ray, the cells were highly resistant to adriamycin-induced apoptosis. This study shows that irradiation inhibited apoptosis by enhancing Bcl-2, attenuating Bax induction, and preventing collapse of mitochondrial membrane potential (delta psi), cytochrome c release into cytoplasm and caspase-3, -6 and -9 activations. In addition, the preirradiation stimulated the activity of manganese-superoxide dismutase (Mn-SOD) and the expression of Mn-SOD mRNA and protein. Adriamycin decreased Mn-SOD activity but did not change the activity of copper/zinc (Cu/Zn)-SOD under either pre- or nonirradiated condition. Phosphothioate-linked antisense against Mn-SOD, which specifically knocked down the activity of Mn-SOD but not that of Cu/Zn-SOD, reversed irradiation-induced protective effect in adriamycin-exposed cardiomyocytes. These data suggest that the irradiation-induced expression of Mn-SOD plays an important role in irradiation-mediated protection in adriamycin-exposed rat ventricular cardiomyocytes.
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PMID:Radiation protects adriamycin-induced apoptosis. 1611 6

The transcription factor nuclear factor kappa-B (NF-kappaB) is involved in regulating responses of neurons to activation of several different signaling pathways in a variety of physiological and pathological settings. During development of the nervous system NF-kappaB is activated in growing neurons by neurotrophic factors and can induce the expression of genes involved in cell differentiation and survival. In the mature nervous system NF-kappaB is activated in synapses in response to excitatory synaptic transmission and may play a pivotal role in processes such as learning and memory. NF-kappaB is activated in neurons and glial cells in acute neurodegenerative conditions such as stroke and traumatic injury, as well as in chronic neurodegenerative conditions such as Alzheimer's disease. Activation of NF-kappaB in neurons can promote their survival by inducing the expression of genes encoding anti-apoptotic proteins such as Bcl-2 and the antioxidant enzyme Mn-superoxide dismutase. On the other hand, by inducing the production and release of inflammatory cytokines, reactive oxygen molecules and excitotoxins, activation of NF-kappaB in microglia and astrocytes may contribute to neuronal degeneration. Emerging findings suggest roles for NF-kappaB as a mediator of effects of behavioral and dietary factors on neuronal plasticity. NF-kappaB provides an attractive target for the development of novel therapeutic approaches for a range of neurological disorders.
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PMID:NF-kappaB in the survival and plasticity of neurons. 1618 23

Previous studies have shown that injection of D-galactose could result in senescent performances in animals, that injection of NaNO2 could cause ischaemia and hypoxia in many organs, and combined injection of D-galactose and NaNO2 make normal mice taking on senescent performances in a shorter period. The aim of this study was to investigate the effects of CE, an extract from a Tibetan medicinal herb, Coeloglossum. viride (L.) Hartm. var. bracteatum (Willd.), on senescent mice. The step-down test was performed to evaluate the learning and memory function of mice. The activities of superoxide dismutase, adenosine triphosphatase, monoamine oxydase and the content of malondialdehyde were measured to determine the impairment of brain. The expressions of Bcl-2, Bax, and caspase-3 proteins in mouse hippocampus were studied by immunohistochemical staining. The data demonstrated that D-galactose and NaNO2 treated mice had significant deficits in learning and memory function. The reduced activities of superoxide dismutase, adenosine triphosphatase, increased activities of monoamine oxydase and level of malondialdehyde were also found. Bax and caspase-3 positive cells increased while Bcl-2 positive cells decreased remarkably. Treatment of CE (2.5, 5 mg.kg(-1)) ameliorated the memory impairment; rectified the biochemistry and neural system changes in mice. These results suggest that CE offers promise as a tool for treatment of senescence-related diseases.
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PMID:Effects of Coeloglossum. viride var. bracteatum extract on memory deficits and pathological changes in senescent mice. 1643 92

We examined the contribution of apoptosis- and oxidative stress-associated genes to apoptosis induction in trophoblast cells of human fetal membrane tissues undergoing apoptosis during in vitro incubation. RT-PCR analyses demonstrated an increased level of HO-1, Mn-SOD, Cox-2, iNOS, TNFalpha, TNFR1, IL-1beta, IL-6, Bax, Bak, and Bad gene expression, while Bcl-2 mRNA expression level decreased. Western blot analyses demonstrated an increase in iNOS, Cox-2, and HO-1 protein levels; a decrease in pro-caspase-3 and 9, proform-PARP, and Apaf-1 protein levels; a leakage of cytochrome c from the mitochondria. An antioxidative reagent, general and selective Cox-2 inhibitors, and an iNOS inhibitor suppressed in vitro progression of the apoptosis. Furthermore, an NO donor reagent induced apoptosis in primary cultured trophoblast cells. Therefore, we concluded that the induction of apoptosis in the smooth chorion trophoblasts is mediated through oxidative stress induction followed by mitochondria damage, suggesting that iNOS and Cox-2 play an important role in the apoptosis induction in trophoblasts of human fetal membrane tissues.
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PMID:Contribution of inducible nitric oxide synthase and cyclooxygenase-2 to apoptosis induction in smooth chorion trophoblast cells of human fetal membrane tissues. 1644

In this article, we studied the chemopreventive effects of sanguinarine on UVB-mediated responses in human HaCaT immortalized keratinocytes. For our studies, HaCaT cells were treated with a low dose (50 nmol/L) of sanguinarine for 24 hours followed by irradiation with UVB (15 or 30 mJ/cm2). Our data showed that UVB exposure, at both doses, resulted in decreased cell viability and increased apoptosis. Interestingly, pretreatment of the cells with sanguinarine caused a significant enhancement in the antiproliferative response of UVB. These responses on UVB and/or sanguinarine treatments were associated with (a) decrease in Bcl-2 and Bcl-X(L) and (b) increase in Bax, Bid, and Bak protein levels. Bax knockdown and Bcl-2 overexpression resulted in a rescue of HaCaT cells from sanguinarine-mediated apoptosis. DNA cell cycle analysis revealed that UVB treatment resulted in an accumulation of cells in the G2-M phase of the cell cycle, whereas pretreatment of sanguinarine resulted in a significant shift of cells in the S phase at a low UVB dose and a further accumulation of cells in the G2-M phase at a higher UVB dose. These effects on cell cycle were accompanied with modulations in the protein levels of cyclin (B1, E, and A) and cdc2 and cyclin-dependent kinase 1. Furthermore, sanguinarine treatment was found to result in significant modulations in p53, p66Shc, MsrA, and superoxide dismutase levels. Based on our data, we suggest the sanguinarine may protect skin cells from UVB-mediated damages via apoptotic elimination of damaged cells that escape programmed cell death and therefore possess a potential of clonal expansion.
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PMID:Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. 1650 17

The anti-cancer effects and possible mechanisms of the freshwater clam (Corbicula fluminea Muller) and its active compounds (FME) on cell viability in human leukemia HL-60 cells were investigated. This study demonstrated that FME was able to inhibit cell proliferation in a concentration- and time-dependent manner. Treatment with FME caused induction of caspase-2, caspase-3, caspase-6, caspase-8, and caspase-9 activity in a time-dependent manner, but not affect caspase-1 activity; it induced the proteolysis of DNA fragmentation factor (DFF-45) and poly(ADP-ribose) polymerase (PARP). Induction of cell death by FME was completely prevented by a pan-caspase inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) and a caspase-2 inhibitor, Z-Val-Asp-Val-Ala-Asp-FMK (Z-VDVAD-FMK). Furthermore, treatment with FME caused a rapid loss of mitochondrial transmembrane potential, stimulation of generation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and GSH depletion. Anti-oxidants such as N-acetylcysteine, catalase, superoxide dismutase, allopurinol, and pyrrolidine dithiocarbamate, but not diphenylene iodonium, significantly inhibited FME-induced cell death. In addition, the results showed that FME-induced apoptosis was accompanied by up-regulation of Bax and Bad, and down-regulation of Bcl-2 and Bcl-XL. Taken together, induction of apoptosis on HL-60 cells by FME was mainly associated with ROS production, GSH depletion, mitochondrial dysfunction, and caspase activation.
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PMID:Apoptosis-inducing active components from Corbicula fluminea through activation of caspase-2 and production of reactive oxygen species in human leukemia HL-60 cells. 1654 98

1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome characterized by elevation of intracellular reactive oxygen species level and apoptotic death. Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity with liver and muscle as target organs. Adiponectin can also suppress superoxide generation in endothelial cells. In the present study, we investigated the protective effects of adiponectin on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Our results suggest that the protective effects of adiponectin on MPP+-induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase, and regulation of Bcl-2 and Bax expression. These data indicated that adiponectin might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease.
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PMID:Adiponectin protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. 1655 29


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