Document Detail


Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation.
MedLine Citation:
PMID:  20716276     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway. The oncogenic potential of Bcl-2 is well established, with its overexpression reported in various cancers. The antiapoptotic function of Bcl-2 is closely associated with its expression levels. Reactive oxygen and nitrogen species (ROS/RNS) are important intracellular signaling molecules that play a key role in various physiological processes including apoptosis. We have recently reported that ROS and RNS can regulate Bcl-2 expression levels, thereby impacting its function. Superoxide anion (*O(2)(-)) plays a proapoptotic role by causing downregulation and degradation of Bcl-2 protein through the ubiquitin-proteasomal pathway. In contrast, nitric oxide (NO)-mediated S-nitrosylation of Bcl-2 prevents its ubiquitination and subsequent proteasomal degradation, leading to inhibition of apoptosis. Interestingly, NO-mediated S-nitrosylation and stabilization of Bcl-2 protein was the primary mechanism involved in the malignant transformation of nontumorigenic lung epithelial cells in response to long-term carcinogen exposure. We describe a novel mechanism of Bcl-2 regulation by *O(2)(-) and NO, providing a new dimension to reactive species-mediated Bcl-2 stability, apoptotic cell death, and cancer development.
Authors:
Neelam Azad; Anand Iyer; Val Vallyathan; Liying Wang; Vincent Castranova; Christian Stehlik; Yon Rojanasakul
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1203     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-18     Completed Date:  2010-09-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia, USA. neelam.azad@hamptonu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Cell Death / genetics
Cell Survival / genetics
Cell Transformation, Neoplastic / genetics,  metabolism*,  pathology
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms / genetics,  metabolism*,  pathology
Oxidative Stress* / genetics
Proto-Oncogene Proteins c-bcl-2 / biosynthesis,  genetics,  metabolism*,  physiology
Reactive Nitrogen Species / genetics,  physiology*
Superoxides / metabolism*
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Nitrogen Species; 11062-77-4/Superoxides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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