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

Neelam Azad*, Anand Iyer, Val Vallyathan, Liying Wang, Vincent Castranova, Christian Stehlik, Yon Rojanasakul

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contribution

89 Scopus citations

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 (·O2-) 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.

Original languageEnglish (US)
Title of host publicationOxidative/Nitrosative Stress and Disease
PublisherBlackwell Publishing Inc.
Pages1-6
Number of pages6
ISBN (Print)9781573317849
DOIs
StatePublished - Aug 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1203
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Bcl-2
  • apoptosis
  • malignant transformation
  • nitric oxide
  • superoxide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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