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

Details

• Personal Author:
  Azad NG ; Castranova, Vincent ; Iyer A ; Rojanasakul Y ; Stehlik C ; Vallyathan V ; Wang L
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Lung Neoplasms Nitrogen Oxides Occupational Health Pathology Respiratory System Safety
• Keywords:
  Apoptosis Author Keywords: Bcl-2 Cancer Cell-damage Cell-transformation Cellular-reactions Gene-mutation Lung-cells Malignant-neoplasms Malignant Transformation Nitric Oxide Nitrogen-oxides Oncogenic-agents Oxidative-processes Oxides Physiological-response Proteins Superoxide Tumors

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• ISSN:
  0077-8923
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; OSHA Region 3 ; OSHA Region 5 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-6
• Volume:
  1203
• NIOSHTIC Number:
  nn:20037951
• Citation:
  Ann NY Acad Sci 2010 Aug; 1203:1-6
• Contact Point Address:
  Neelam Azad, Ph.D., Kittrell Hall, Queen and Tyler Streets, Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668
• Email:
  neelam.azad@hamptonu.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Oxygen (CAS RN 7782-44-7)
• Federal Fiscal Year:
  2010
• Peer Reviewed:
  True
• Source Full Name:
  Annals of the New York Academy of Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6166dc84f0e6bfdb02183e301d3641cf2db1b146789ad7152e6ce15573feeaadd67500a53c06e1c570918507e77eb0c4780ae7a9f6dfa3b477f706309db0b377
• Download URL:
  https://stacks.cdc.gov/view/cdc/191855/cdc_191855_DS1.pdf
• File Type:
  [PDF - 211.83 KB ]