Article

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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    • "to four BH domains (BH1–4; Kuwana and Newmeyer, 2003; Hardwick and Youle, 2009; Akl et al., 2014). Protein factors possessing all four BH domains, including Mcl-1L, antagonize apoptosis by preventing drugs that can restore cell death susceptibility in tumor cells (Fesik, 2005). "
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    ABSTRACT: The Bcl-2 (B-cell lymphoma-2) family proteins are critical regulators of apoptosis and consist of both pro- and anti-apoptotic factors. Within this family, the myeloid cell leukemia factor 1 (Mcl-1) protein exists in two forms as the result of alternative splicing. The long variant (Mcl-1L) acts as an anti-apoptotic factor, whereas the short isoform (Mcl-1S) displays pro-apoptotic activity. In this study, using splice-switching antisense oligonucleotides (ASOs), we increased the synthesis of Mcl-1S, which induced a concurrent reduction of Mcl-1L, thus resulting in the increased sensitivity of cancer cells to apoptotic stimuli. The Mcl-1 ASOs also induced mitochondrial hyperpolarization and a consequent increase in mitochondrial calcium (Ca2+) accumulation. The high Mcl-1S/L ratio was correlated with significant hyperfusion of the entire mitochondrial network, which occurred in a Dynamin-related protein (Drp1)-dependent manner. Our data indicate that the balance between the long and short variants of the Mcl-1 gene represents a key aspect of the regulation of mitochondrial physiology. Moreover, we propose that the Mcl-1L/S balance is a novel regulatory factor controlling the mitochondrial fusion and fission machinery.
    No preview · Article · Oct 2015 · Molecular biology of the cell
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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.
    Full-text · Article · Sep 2014 · Nutrition & Diabetes
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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 (http://bcl2db.ibcp.fr) 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: http://bcl2db.ibcp.fr
    Full-text · Article · Jan 2014 · Database The Journal of Biological Databases and Curation
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