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Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation.

Authors
Azad-NG; Iyer-A; Vallyathan-V; Wang-L; Castranova-V; Stehlik-C; Rojanasakul-Y
Source
Ann NY Acad Sci 2010 Aug; 1203:1-6
NIOSHTIC No.
20037951
Abstract
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.
Keywords
Oncogenic-agents; Proteins; Tumors; Pathology; Oxidative-processes; Malignant-neoplasms; Cancer; Gene-mutation; Nitrogen-oxides; Oxides; Cell-transformation; Cellular-reactions; Physiological-response; Cell-damage; Lung-cells; Author Keywords: Bcl-2; nitric oxide; superoxide; apoptosis; malignant transformation
Contact
Neelam Azad, Ph.D., Kittrell Hall, Queen and Tyler Streets, Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668
CODEN
ANYAA9
CAS No.
7782-44-7; 10102-43-9
Publication Date
20100801
Document Type
Journal Article
Email Address
neelam.azad@hamptonu.edu
Fiscal Year
2010
NTIS Accession No.
NTIS Price
ISSN
0077-8923
NIOSH Division
HELD
Source Name
Annals of the New York Academy of Sciences
State
VA; WV; IL
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