| Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation. | |
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MedLine Citation:
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PMID: 20716276 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Neelam Azad; Anand Iyer; Val Vallyathan; Liying Wang; Vincent Castranova; Christian Stehlik; Yon Rojanasakul |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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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:
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Created Date: 2010-08-18 Completed Date: 2010-09-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1-6 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, Virginia, USA. neelam.azad@hamptonu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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