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)

Synaptogenesis in humans occurs in the last trimester of gestation and in the first few years of life, whereas it occurs in the postnatal period in rodents. A single exposure of neonatal rodents to ethanol during this period evokes extensive neuronal apoptosis. Previous studies indicate that ethanol triggers the intrinsic apoptotic pathway in neurons, and that this requires the multi-BH domain, proapoptotic Bcl-2 family member Bax. To define the upstream regulators of this apoptotic pathway, we examined the possible roles of p53 and a subclass of proapoptotic Bcl-2 family members (i.e. the BH3 domain-only proteins) in neonatal wild-type and gene-targeted mice that lack these cell death inducers. Acute ethanol exposure produced greater caspase-3 activation and neuronal apoptosis in wild-type mice than in saline-treated littermate controls. Loss of p53-upregulated mediator of apoptosis (Puma) resulted in marked protection from ethanol-induced caspase-3 activation and apoptosis. Although Puma expression has been reported to be regulated by p53, p53-deficient mice exhibited a similar extent of ethanol-induced caspase-3 activation and neuronal apoptosis as wild-type mice. Mice deficient in other proapoptotic BH3-only proteins, including Noxa, Bim, or Hrk, showed no significant protection from ethanol-induced neuronal apoptosis. Collectively, these studies indicate a p53-independent, Bax- and Puma-dependent mechanism of neuronal apoptosis and identify Puma as a possible molecular target for inhibiting the effects of intrauterine ethanol exposure in humans.
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PMID:The proapoptotic BH3-only, Bcl-2 family member, Puma is critical for acute ethanol-induced neuronal apoptosis. 1953 97

Earlier studies from this and other laboratories show that ethanol induces apoptotic death of fetal and neonatal neurons. One mechanism that underlies these effects is the ethanol-associated reduction in the phosphatidylinositol 3' kinase pro-survival pathway. Another mechanism involves the oxidative stress caused by the ethanol-associated increase in reactive oxygen species (ROS). In the present study, we used the murine HN2-5 hippocampal-derived cell line to investigate the effects of ethanol on ROS levels and apoptosis. We also investigated the potential neuroprotective effects of two structurally unrelated antioxidants: N-acetylcysteine (NAC) and melatonin. The results demonstrate that NAC blocked an ethanol-associated increase in ROS. In addition, NAC and melatonin prevented the augmentation of apoptosis in ethanol-treated neurons. Both antioxidants significantly elevated the expression of the anti-apoptotic gene XIAP in ethanol-treated and/or control neurons and melatonin increased Bcl-2 expression in ethanol-treated neurons. Thus, it is possible that the neuroprotective effects of NAC and melatonin involve their ability to augment the expression of one or more anti-apoptotic gene as well as their classical antioxidant actions. Additional studies are needed to establish the effectiveness of these antioxidants to prevent the loss of neurons which accompanies in utero exposure to ethanol.
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PMID:Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells. 1953 46

Thymosin-beta4 (Tbeta4) is a major actin monomer-binding peptide in mammalian tissues and plays a crucial role in the nervous system in synaptogenesis, neuronal survival and migration, axonal growth, and plastic changes of dendritic spines. However, it is unknown whether Tbeta4 is also involved in challenges with external stress such as ethanol-induced neurotoxicity. In the present study, we investigated the effects of Tbeta4 on ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes and the underlying mechanisms. Primarily cultured astrocytes were treated with 1 microg/ml Tbeta4 2 h prior to administration of 100 mM ethanol for 0.5, 1, 3 and 6 days, respectively. The results showed that ethanol caused neurotoxicity in cultured astrocytes, as shown by declined cell viability, distinct astroglial apoptosis and increased intracellular peroxidation. Tbeta4 markedly promoted cell viability, ameliorated the injury of intracellular glial fibrillary acidic protein-immunopositive cytoskeletal structures, reduced the percentage of apoptotic astrocyte and cellular DNA fragmentation, suppressed caspase-3 activity and upregulated Bcl-2 expression, inhibited the accumulation of reactive oxygen species and production of malondialdehyde in ethanol-treated astrocytes in a time-dependent manner. These data indicated that Tbeta4 attenuates ethanol-induced neurotoxicity in cultured cortical astrocytes through inhibition of apoptosis signaling, and one of the mechanisms underlying the capacity of Tbeta4 to suppress apoptosis may in part be due to its effect of anti-peroxidation.
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PMID:Thymosin-beta4 attenuates ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes by inhibiting apoptosis. 1968 60

The leaves and roots of Alpinia pricei Hayata are used as a traditional wrapping for food and as a cooking substitute for fresh ginger. Our previous study showed that ethanol extracts from the roots of A. pricei Hayata (EEAP) and its phenolic compounds have anti-inflammatory effects. The aims of this work were to further study the in vitro anticancer activity of EEAP and its active compounds with respect to various cancer cells. The results from an MTT assay demonstrated that EEAP decreased the cell population growth of CH27, HL-60, and A549 cells. Flow cytometric analysis of HL-60 cells exposed to EEAP showed that the number of apoptotic cells increased in a time- and dose-dependent manner. Western blot data revealed that EEAP stimulated an increase in the level of protein expression of Fas, FasL, caspase-8, and tBid. Moreover, the ratio of the expression levels of pro- and anti-apoptotic Bcl-2 family members was changed after treatment with EEAP. EEAP-induced apoptosis involved the release of mitochondrial cytochrome c and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase (PARP). The results also demonstrated that phenolic compounds (caffeic acid, apigenin, curcumin, and pinocembrin) from EEAP decreased the rate of population growth of HL-60 cells. Treatment of HL-60 cells with these phenolic compounds caused the loss of mitochondrial membrane potential. Our finding could provide critical information regarding the chemopreventive potential of ethanol extracts from A. pricei Hayata. These results also demonstrate that the EEAP-induced apoptotic ability in HL-60 cells might be related to the phenolic compounds.
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PMID:Anticancer effects of Alpinia pricei Hayata roots. 2002 79

Alcohol is known to impede the growth of the central nervous system and to induce neurodegeneration through cellular apoptosis. We have previously shown that moderate prenatal alcohol exposure results in brain defects at different stages of development. In this study, we further characterize the proteomic architecture underlying ethanol teratogenesis during early fetal brain development using chromatography in conjunction with a LC-MS/MS system. Pregnant C57BL/6 mice were exposed from embryonic day 7 (E7) to E13 with either a 25% ethanol derived calorie or pair-fed liquid diets. At E13, fetal brains were collected from five dams for each group. Individual brains were homogenized and the extracted proteins were then tryptically digested and analyzed by LC-MS/MS. Label-free quantitative proteomic analyses were performed on proteomes extracted from fetal brains of both alcohol-treated (ALC) and pair-fed groups. These analyses demonstrated that prenatal alcohol exposure induced significant downregulation (p<0.001) of the expression of mitochondrial enzymes including ADP/ATP translocase 1, ATP synthase subunit alpha and ubiquinol-cytochrome-c reductases. In addition, mitochondrial carrier homolog 1, which plays a role in apoptosis, was significantly downregulated (p<0.001) in the ALC group. Moreover, among the cytosolic proteins that were significantly downregulated (p<0.001) are Bcl-2, 14-3-3 protein and calmodulin. Significant downregulation (p<0.001) of proteins that are critical for fetal brain development was observed such as prohibitin and neuronal migration protein doublecortin. These findings provide information about possible mechanisms underlying the effects of prenatal alcohol exposure during early embryonic stage.
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PMID:Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation. 2011 57

The objective of this study was to explore the effects of Gynostemma pentaphyllum on Zearalenone-induced apoptosis in mouse male germ cells. Fifty Kunming male mice at 25-days-old were classified into five groups: group A was the control (10% ethanol, 0.5 ml/day); group B with 10 microg Zearalenone/day; group C with 10 microg Zearalenone and 50 mg/kg/day Gynostemma pentaphyllum; group D with 10 microg Zearalenone and 100 mg/kg/day Gynostemma pentaphyllum; and group E with 10 microg Zearalenone and 200 mg/kg/day Gynostemma pentaphyllum. It was found that Gynostemma pentaphyllum has a marked effect on protecting male germ cells against Zearalenone-induced apoptosis, as evidenced by a reduced apoptosis rate of male germ cells and Bax expression as well as an enhancement of Bcl-2 expression in Gynostemma pentaphyllum-treated groups compared to the control. In addition, Gynostemma pentaphyllum remarkably improved pathologic changes of testicular tissue, reduced the content of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) caused by Zearalenone. Taken together, these results suggest that Gynostemma pentaphyllum protects against toxicity caused by Zearalenone through anti-oxidation and anti-apoptosis via the regulation of Bax and Bcl-2 expression.
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PMID:Gynostemma pentaphyllum protects mouse male germ cells against apoptosis caused by zearalenone via Bax and Bcl-2 regulation. 2016 93

Parkinson's disease (PD), one of the most common neurodegenerative disorders, is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) to the striatum (ST), and involves oxidative stress. Mulberry fruit from Morus alba L. (Moraceae) is commonly eaten, and has long been used in traditional oriental medicine. It contains well-known antioxidant agents such as anthocyanins. The present study examined the protective effects of 70 % ethanol extract of mulberry fruit (ME) against neurotoxicity in in vitro and in vivo PD models. In SH-SY5Y cells stressed with 6-hydroxydopamine (6-OHDA), ME significantly protected the cells from neurotoxicity in a dose-dependent manner. Other assays demonstrated that the protective effect of ME was mediated by its antioxidant and anti-apoptotic effects, regulating reactive oxygen species and NO generation, Bcl-2 and Bax proteins, mitochondrial membrane depolarisation and caspase-3 activation. In mesencephalic primary cells stressed with 6-OHDA or 1-methyl-4-phenylpyridinium (MPP+), pre-treatment with ME also protected dopamine neurons, showing a wide range of effective concentrations in MPP+-induced toxicity. In the sub-acute mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), ME showed a preventative effect against PD-like symptoms (bradykinesia) in the behavioural test and prevented MPTP-induced dopaminergic neuronal damage in an immunocytochemical analysis of the SNpc and ST. These results indicate that ME has neuroprotective effects in in vitro and in vivo PD models, and that it may be useful in preventing or treating PD.
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PMID:Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson's disease models. 2018 87

Alcohol consumption increases apoptosis of hepatocytes. Death of hepatocytes is a characteristic feature of chronic liver disease for various causes. Bee venom (Apis mellifera) has been traditionally used for the treatment of various chronic diseases, such as chronic inflammatory arthritis and chronic liver disease. However, the precise mechanism for bee venom in chronic liver disease is not still cleared. To assess the effects of bee venom in chronic liver disease, we investigated the potential role of the bee venom in the ethanol-induced hepatocyte apoptosis. Bee venom treatment inhibited the apoptotic cell morphology and increased the cell viability in ethanol-induced hepatocyte apoptosis. With ethanol treatment, bee venom-treated hepatocytes increased activity of Bcl-2 and Bcl-xL, reduced activity of Bax, Caspase and PARP. In conclusion, bee venom treatment in ethanol-induced hepatocyte apoptosis occurred through the regulation of Bcl family with subsequent inactivation of the Caspase and PARP. These results suggest that bee venom could be an effective agent to reduce ethanol-induced hepatocyte apoptosis.
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PMID:The protective effect of bee venom against ethanol-induced hepatic injury via regulation of the mitochondria-related apoptotic pathway. 2021 Jul 90

Apoptosis inhibition has been reported in the male reproductive tract of teleost fish exposed to 17beta-estrogen or estrogen-like compounds. In order to understand the molecular mechanisms of cell death inhibition, this study examined 2 genes involved in the apoptotic pathway, Bcl-2 and Caspase 3, an anti-apoptotic and a pro-apoptotic genes, respectively. Partial cDNA sequences of Bcl-2 and Caspase 3 were cloned from gudgeon (Gobio gobio), a common European cyprinid fish. To follow mRNA levels of Bcl-2 and Caspase 3 under xenoestrogen exposure, we first performed an in vitro experiment on fish testis exposed to the most potent xenoestrogen found in the environment, ethinylestradiol (EE2). We further studied mRNA expression of both genes in the testis of fish exposed to xenoestrogens in situ. In the in vitro experiment, fragments of gudgeon testis were exposed for 21 days to 10(-3), 10(-2), 10(-1), 1 and 10 microg/L of EE2, as well as to positive (10(-1) microg/L of E2) and ethanol control medium. Results showed a significant induction of Bcl-2 mRNA at 10(-1) microg/L (p<0.05). Surprisingly, Caspase 3, a cell death effector, displayed the same profile as observed for the anti-apoptotic gene Bcl-2. In the experiment on wild gudgeon exposed from birth to an estrogenic sewage treatment plant effluent, the mRNA expression of Bcl-2 and Caspase 3 in feminized fish (ovotestis) was not significantly different due to high variability of expression between individuals. At the current state of knowledge on spermatogenesis disruption in teleost fish, in vitro studies seem better adapted than in situ investigations to enlighten the molecular pathway of apoptosis inhibition in testis exposed to xenoestrogens.
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PMID:Bcl-2 and Caspase 3 mRNA levels in the testes of gudgeon, Gobio gobio, exposed to ethinylestradiol (EE2). 2035 36

To study the anti-tumor activity of Scurrula parasitica polysaccharides (SP). Water extraction and ethanol precipitation were used to isolate SP from S. parasitica leaf. S180, K562 and HL-60 cell lines proliferation inhibition by SP were detected by MTT assay. The expressions of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP+ SP could not inhibit cancer cell proliferation. SP ip could inhibit the growth of sarcoma S180 in mice, 100 mg x kg(-1) x d(-1). SP ip was the optimal dose on inhibiting S180 growth, with the tumor inhibition rate of 54%. The expression of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP. The result showed that SP could down-regulate the expression of Ki-67, CyclinD1 and Bcl-2 protein, and up-regulate the expression of Bax protein. It indicted that inhibiting cancer cell proliferation and promoting cancer cell apoptosis in vivo maybe one of the anti-cancer mechanisms of SP.
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PMID:[Polysaccharides from Scurrula parasitica L. inhibit sarcoma S180 growth in mice]. 2042 11


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