Snapshot: Bcl2 proteins

Johns Hopkins, Baltimore, MD 21205, USA.
Cell (Impact Factor: 32.24). 08/2009; 138(2):404, 404.e1. DOI: 10.1016/j.cell.2009.07.003
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Available from: J. Marie Hardwick,
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    • "Apoptosis, known as programmed cell death, is regulated by the Bcl-2 family of proteins.26 In addition, a report shows that under hydrogen peroxide treatment Bcl-2 proteins cooperatively function in response to oxidative stress-induced apoptosis.27 "
    Y Fang · Q Zhang · J Tan · L Li · X An · P Lei ·
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    ABSTRACT: Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS), a common sleep and breathing disorder, is independently associated with metabolic dysfunction, including impaired glucose tolerance and insulin resistance. Intermittent hypoxia (IH), a pathological component of OSAHS, increases oxidative stress damage to pancreatic β-cells in animal models resembling patients with OSAHS. However, the precise mechanisms of IH-induced pancreatic β-cell dysfunction are not fully understood. In the present study, we established a mice model to investigate the underlying mechanisms of oxidative stress in IH-induced pancreatic β-cell apoptosis through antioxidant N-acetylcysteine (NAC) pretreatment. Methods: Twenty-four Wistar rats were randomly divided into four experimental groups: normal control group, intermittent normoxia group, IH group and antioxidant intervention group. Pancreatic β-cell apoptosis rates were detected by terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling; Bcl-2 and Bax protein expressions were detected by immunohistochemistry staining and western blotting. Results: In our study, we demonstrated that IH exposure causes an increased activation of pancreatic β-cell apoptosis compared with that in the normal control group and intermittent normoxia group, accompanied by the downregulation of Bcl-2 and upregulation of Bax (P<0.05). Furthermore, compared with the IH group, antioxidant (NAC) pretreatment significantly decreased IH-mediated β-cell apoptosis and reversed the ratio of Bcl-2/Bax expression (P<0.05). Conclusion: Taken together, these results demonstrate a critical role of oxidative stress in the regulation of apoptosis through Bcl-2 and Bax signaling. The antioxidant NAC has a protective effect against IH-induced pancreatic β-cell apoptosis.
    Nutrition & Diabetes 09/2014; 4(9):e131. DOI:10.1038/nutd.2014.28 · 2.65 Impact Factor
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    • "Bax, Bak and Bid), whereas all of the BH3-only proteins are pro-apoptotic. Moreover, a variety of viral proteins have been found to be structurally similar to BCL-2 with or without obvious sequence similarity (3). "
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    ABSTRACT: BCL2DB ( is a database designed to integrate data on BCL-2 family members and BH3-only proteins. These proteins control the mitochondrial apoptotic pathway and probably many other cellular processes as well. This large protein group is formed by a family of pro-apoptotic and anti-apoptotic homologs that have phylogenetic relationships with BCL-2, and by a collection of evolutionarily and structurally unrelated proteins characterized by the presence of a region of local sequence similarity with BCL-2, termed the BH3 motif. BCL2DB is monthly built, thanks to an automated procedure relying on a set of homemade profile HMMs computed from seed reference sequences representative of the various BCL-2 homologs and BH3-only proteins. The BCL2DB entries integrate data from the Ensembl, Ensembl Genomes, European Nucleotide Archive and Protein Data Bank databases and are enriched with specific information like protein classification into orthology groups and distribution of BH motifs along the sequences. The Web interface allows for easy browsing of the site and fast access to data, as well as sequence analysis with generic and specific tools. BCL2DB provides a helpful and powerful tool to both ‘BCL-2-ologists’ and researchers working in the various fields of physiopathology.Database URL:
    Database The Journal of Biological Databases and Curation 01/2014; 2014:bau013. DOI:10.1093/database/bau013 · 3.37 Impact Factor
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    • "Conversely, c-FLIP competes with caspase-8 for binding to the DISC complex but is devoid of caspase activity, thus precluding caspase-8 activation in a dominant negative manner [14]. Mitochondrial apoptosis pathway is controlled at the level of the mitochondrial outer membrane integrity, which is tightly regulated by members of BCL-2 protein family such as prosurvival BCL-2 and BCL-xL in addition to proapoptotic BAX and BAK [15]. In particular, a decrease in the ratio of prosurvival to proapoptotic BCL-2 family proteins leads to the disruption of the mitochondrial outer membrane and consequent cytosolic release of cytochrome c to form the apoptosome complex with Apaf-1 for caspase-9 activation [16] [17]. "
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    ABSTRACT: Subamolide B is a butanolide isolated from Cinnamomum subavenium, a medicinal plant traditionally used to treat various ailments including carcinomatous swelling. We herein reported for the first time that subamolide B potently induced cytotoxicity against diverse human skin cancer cell lines while sparing nonmalignant cells. Mechanistic studies on human cutaneous squamous cell carcinoma (SCC) cell line SCC12 highlighted the involvement of apoptosis in subamolide B-induced cytotoxicity, as evidenced by the activation of caspases-8, -9, -4, and -3, the increase in annexin V-positive population, and the partial restoration of cell viability by cotreatment with the pan-caspase inhibitor z-VAD-fmk. Additionally, subamolide B evoked cell death pathways mediated by FasL/Fas, mitochondria, and endoplasmic reticulum (ER) stress, as supported by subamolide B-induced FasL upregulation, BCL-2 suppression/cytosolic release of cytochrome c, and UPR activation/CHOP upregulation, respectively. Noteworthy, ectopic expression of c-FLIPL or dominant-negative mutant of FADD failed to impair subamolide B-induced cytotoxicity, whereas BCL-2 overexpression or CHOP depletion greatly rescued subamolide B-stimulated cells. Collectively, these results underscored the central role of mitochondrial and CHOP-mediated cell death pathways in subamolide B-induced cytotoxicity. Our findings further implicate the potential of subamolide B for cutaneous SCC therapy or as a lead compound for developing novel chemotherapeutic agents.
    Evidence-based Complementary and Alternative Medicine 03/2013; 2013:630415. DOI:10.1155/2013/630415 · 1.88 Impact Factor
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