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)

The relationship between expression of genes encoding key antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and change in production of reactive oxygen species (ROS) resulting from development of resistance of cancer cells K562, MCF-7, and SKOV-3 to the prooxidant chemotherapeutic agent doxorubicin (DOX) has been studied. Significant increase in mRNA level and activity of Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase-1 (GPx-1) and reduced ROS level was found in resistant K562/DOX and SKVLB cells. In contrast, no change in ROS level was observed in MCF-7/DOX cells in parallel with decrease in Mn-SOD and catalase mRNAs and corresponding activities concurrently with high increase in GPx-1 mRNA and activity. As a result of the development of resistance, a similarity was found between the change in ROS level and the change in ho-1 and bcl-2 gene expression, whereas elevation of bcl-xl gene expression was observed in all three types of resistant cells. Particular features of development of adaptive antioxidant response as well as redox-dependent change in bcl-2 gene expression under formation of DOX resistance of cancer cells of different genesis are discussed.
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PMID:Changes in expression of genes encoding antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and in level of reactive oxygen species in tumor cells resistant to doxorubicin. 1714 Mar 81

Oxidative stress has been linked with apoptosis in germ cells and with male infertility. However, the molecular mechanism of oxidative-stress-mediated apoptosis in germ cells has not been clearly defined so far. Because of the involvement of CDC2 and cyclin B1 in cell cycle regulation and their plausible role in apoptosis, the present study aimed to investigate the possibility that selenium (Se)-induced oxidative-stress-mediated modulations of these cell cycle regulators cause DNA damage and apoptosis in germ cells. To create different Se status (deficient, adequate and excess), male Balb/c mice were fed yeast-based Se-deficient diet (Group I) and a deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se in Groups II and III, respectively) for a period of 8 weeks. After the completion of the diet feeding schedule, a significant decrease in Se levels and glutathione peroxidase activity was observed in the Se-deficient group (Group I), whereas the Se-excess group (Group III) demonstrated an increase in Se levels. Increased levels of lipid peroxidation were seen in both Groups I and III when compared to Group II, indicating oxidative stress. The mRNA and protein expressions of both CDC2 and cyclin B1 were found to be significantly decreased in Groups I and III. A decrease in the immunohistochemical localization of these proteins was also observed in spermatogenic cells. The mRNA expressions of apoptotic factors such as Bcl-2, Bax, caspase-3 and caspase-9 were found to be increased in Groups I and III. A decrease in CDC2 kinase activity was also seen in these groups. Increased apoptosis was observed in Group I and Group III animals by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay indicating oxidative-stress-mediated DNA damage. These findings suggest the effect of Se-induced oxidative stress on the cell cycle regulators and apoptotic activity of germ cells, thus providing new dimensions to molecular mechanisms underlying male infertility.
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PMID:Dietary selenium variation-induced oxidative stress modulates CDC2/cyclin B1 expression and apoptosis of germ cells in mice testis. 1732 Mar 65

Selenium (Se) has protective properties against ultraviolet (UV)-induced changes in skin cells in vitro but little is known about such activity in human subjects. In the present study, seven patients with psoriasis ingested 400 microg of sodium selenite daily during a 4 week course of whole-body narrow-band UVB (TL01) therapy while six more psoriasis patients, similarly irradiated, ingested a placebo. Skin biopsies, collected at the start and end of the phototherapy were analysed for phosphorylated p53, Fas, Bcl-2, Bax and oxidized guaninosine, and for numbers of Langerhans and sunburn cells. Following the TL01 therapy, no significant difference was observed for any of these markers when the Se group was compared with the placebo group of patients, although p53 and Bcl-2 expression decreased in the Se supplemented group.
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PMID:Lack of effect of oral selenite on p53 associated gene expression during TL01 therapy of psoriasis patients. 1752 32

The present study was designed to evaluate the apoptotic efficacy of selenium (Se) under glutathione-deprived conditions. Testicular cells were used as a model to assess the above. For the study, cells were maintained for 4 h under various treatments; control (media only), selenium (0.5 microM and 1.5 microM), BSO (20 nM), selenium + BSO (0.5 microM Se + 20 nM BSO and 1.5 microM Se + 20 nM BSO). The treated cells were harvested for various estimations viz. viability, GSH, GSSG, redox ratio, ROS generation and integrity of DNA. mRNA was extracted for RT-PCR analysis of JNK, p38, caspase 3 and Bcl-2. It was observed that the cell viability decreased concomitant with the decrease in GSH levels, increase in GSSG levels and increase in the generation of ROS in the combined treatment group in comparison to control and individual treatments. Also, there was an increase in the mRNA expression of JNK and p38 MAPK along with an increase in caspase 3 expression and decrease in Bcl-2 expression. The integrity of DNA was also found to be altered in the combined treatment. Thus, the results presented in this work agree with those earlier reports in a notion that sodium selenite causes apoptosis and the toxicity of selenite is mediated by increase of intracellular ROS. Also, reduction in endogenous GSH along with selenite treatment is associated with increased apoptosis, increased expression of p38 and JNK MAPK, decreased Bcl-2 expression, and increase in caspase-3 expression. Our data indicates that GSH participates in apoptosis in testicular cells and that depletion of this molecule may be critical in predisposing these cells to apoptotic cell death.
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PMID:Decreased glutathione levels potentiate the apoptotic efficacy of selenium: possible involvement of p38 and JNK MAPKs--in vitro studies. 1798 39

Selenium (Se) is an essential micronutrient as well as a toxic trace element in animal and human nutrition. The effects of Se in the immune system and some diseases are well documented. The objective of the present study was to examine the role of Se in reducing the hypoxia induced apoptosis in neuroblastoma cell line. Hypoxia showed an enhanced cytotoxicity, increased free radical production and apoptosis (p<0.001) which was measured in terms of DNA break down by comet assay. Hypoxia has decreased reduced Glutathione (GSH) content, Glutathione Reductase (GR), Glutathione peroxidase (GPx) and Superoxide Dismutase (SOD) activities as compared to control cells. During hypoxic condition the expression of cytochrome C, pro and active caspase-3 levels were enhanced significantly followed by nonsignificant upregulation of Bcl-2. But, the Se supplementation inhibited the cytotoxicity, free radical generation and stabilized the HIF-1alpha accumulation in cells under hypoxia. The GSH content, GR, GPx and SOD activities increased significantly in Se-treated hypoxic cells, as compared to control. Further there was an appreciable inhibition of apoptosis by upregulation of Bcl-2 proteins, in the presence of Se under hypoxia. Selenium supplementation to cells significantly inhibited the hypoxia induced DNA fragmentation and restored the antioxidant status back to control levels. This study suggests that Se supplementation prevented the cells from hypoxia induced apoptosis by triggering upregulation of Bcl-2 protein and reducing the oxidative stress.
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PMID:Selenium protects the hypoxia induced apoptosis in neuroblastoma cells through upregulation of Bcl-2. 1840 86

The role of selenium as potential cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical and clinical studies. Although cell apoptosis has been evidenced as a critical mechanism mediating the anticancer activity of selenium, the underlying molecular mechanisms remain elusive. In the present study, we showed that selenocystine (SeC), a naturally occurring selenoamino acid, induced caspase-independent apoptosis in MCF-7 breast carcinoma cells, which was accompanied by poly(ADP-ribose) polymerase (PARP) cleavage, caspase activation, DNA fragmentation, phosphatidylserine exposure and nuclear condensation. Moreover, SeC induced the loss of mitochondrial membrane potential (DeltaPsi(m)) by regulating the expression and phosphorylation of Bcl-2 family members. Loss of DeltaPsi(m) led to the mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF) which subsequently translocated into the nucleus and induced chromatin condensation and DNA fragmentation. MCF-7 cells exposed to SeC shown increase in total p53 and phosphorylated p53 on serine residues of Ser15, Ser20, and Ser392 prior to mitochondrial dysfunction. Silencing and attenuating of p53 activation with RNA interference and pifithrin-alpha treatment, respectively, partially suppressed SeC-induced cell apoptosis. Furthermore, generation of reactive oxygen species and subsequent induction of DNA strand breaks were found to be upstream cellular events induced by SeC. The thiol-reducing antioxidants, N-acetylcysteine and glutathione, completely blocked the occurrence of cell apoptosis. Taken together, these results suggest that SeC, as a promising anticancer selenocompound, induces MCF-7 cell apoptosis by activating ROS-mediated mitochondrial pathway and p53 phosphorylation.
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PMID:Selenocystine induces caspase-independent apoptosis in MCF-7 human breast carcinoma cells with involvement of p53 phosphorylation and reactive oxygen species generation. 1871 51

Selenium, an essential trace element, showed the significant protective effects against liver and kidney damage induced by some heavy metals. However, the mechanism how selenium suppresses cadmium (Cd)-induced cytotoxicity remains unclear. In this study, we investigated the protective mechanism of selenium on Cd-induced apoptosis in LLC-PK(1) cells via reactive oxygen species (ROS) and mitochondria linked signal pathway. Studies of PI and Annexin V dual staining analysis demonstrated that 20 microM Cd-induced apoptosis as early as 18 h. A concomitant by the generation of ROS, the loss of mitochondrial membrane potential, cytochrome c (cyt c) release, activation of caspase-9, -3 and regulation of Bcl-2 and Bax were observed. N-acetylcysteine (NAC, 500 microM), a free radical scavenger, was used to determine the involvement of ROS in Cd-induced apoptosis. During the process, selenium played the same role as NAC. The anti-apoptosis exerted by selenium involved the blocking of Cd-induced ROS generation, the inhibition of Cd-induced mitochondrial membrane potential collapse, the prevention of cyt c release, subsequent inhibition of caspase activation and the changed level of Bcl-2 and Bax. Taken together, we concluded that Cd-induced apoptosis was mediated by oxidative stress and selenium produced a significant protection against Cd-induced apoptosis in LLC-PK(1) via ameliorating the mitochondrial dysfunction.
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PMID:The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. 1913 40

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.
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PMID:Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis. 1934 86

Recent studies establish a critical role of selenium in cancer prevention in vitro and in vivo. Selenium may sensitize TRAIL-mediated apoptosis in human renal cancer cells and increase therapeutic efficacy. In this study, we demonstrate that concomitant administration of TRAIL and Se-methylselenocysteine (Se-MSC) produces synergistic effects on the induction of apoptosis in Caki cells. Se-MSC rapidly and specifically down-regulates expression of the Bcl-2 at transcriptional level. The forced expression of Bcl-2 attenuated Se-MSC plus TRAIL-mediated apoptosis, suggesting that the lessened Bcl-2 expression caused by Se-MSC treatment is critical to the increased sensitivity to TRAIL in renal cancer cells. In addition, we demonstrate that the synergistic effects of Se-MSC and TRAIL result from the activation of the caspase-dependent pathways. Co-administration of HA14-1, a small molecule Bcl-2 inhibitor and TRAIL increased apoptosis in Caki cells. Taken together, Se-MSC-mediated down-regulation of Bcl-2 is able to sensitize Caki cells for TRAIL-induced apoptosis. Thus, selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in renal cancer cells.
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PMID:Se-methylselenocysteine sensitized TRAIL-mediated apoptosis via down-regulation of Bcl-2 expression. 1936 Mar 59

Selenium has been linked to cell survival and apoptosis. Apoptosis plays an important role in spermatogenesis. Evidence suggests that reactive oxygen species induce apoptotic pathways. Although the mechanism by which oxidants mediate apoptosis is not well defined, the mitogen-activated protein kinase (MAPK) and caspase pathways have been implicated in apoptosis. Thus, this study was designed, keeping in view the critical balance between cell proliferation and apoptosis for normal spermatogenesis, and the requirement of selenium for the maintenance of male fertility. The intracellular selenium status was modulated by feeding selenium-deficient and -excess diet for 8 weeks. Involvement of p38 MAPK and ROS was monitored. Apoptotic factors like caspases and Bcl-2 were also analyzed. It was observed that the selenium levels were altered along with an increase in ROS generation and lipid peroxidation. mRNA expression of p38, caspases 3, and 8 increased, whereas that for Bcl-2 decreased. Western immunoblot analysis and immunohistochemical localization studies for p38 showed a similar increase. Integrity of DNA was altered in the form of apoptotic cells. Thus, the results presented in this study suggest that sodium selenite causes apoptosis and the toxicity of selenite is mediated by increase in ROS. Morevoer, ROS generation is associated with increased expression of p38, caspases 3 and 8, and decreased Bcl-2 expression. Our data indicate that p38 participates in testicular apoptosis and that selenium is required for maintenance of the critical balance between cell death and proliferation.
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PMID:Apoptosis induced by modulation in selenium status involves p38 MAPK and ROS: implications in spermatogenesis. 1936 75


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