Vanadate Induces p53 Transactivation Through Hydrogen Peroxide and Causes Apoptosis

Details

• Personal Author:
  Butterworth L ; Castranova, Vincent ; Costa M ; Ding M ; Huang C ; Leonard, Stephen S. ; Li J ; Lu Y ; Rojanasakul Y ; Shen H-M ; Shi X ; Vallyathan V ; Ye J ; Zhang Z
• Description:
  Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induced p53 activation and involvement of reactive oxygen species (ROS) in p53 activation as well as the role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6 cells to vanadate led to transactivation of p53 activity in a time- and dose-dependent manner. It also caused mitochondrial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H(2)O(2) by N-acetyl-l-cysteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor), or the chelation of vanadate by deferoxamine, resulted in inhibition of p53 activation and cell mitochondrial damage. In contract, an increase in H(2)O(2) generation in response to superoxide dismutase or NADPH enhanced these effects caused by vanadate. Furthermore, vanadate-induced apoptosis occurred in cells expressing wild-type p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results demonstrate that vanadate induces p53 activation mainly through H(2)O(2) generation, and this activation is required for vanadate-induced apoptosis. [Description provided by NIOSH]
• Subjects:
  Animals Environment Environmental Exposure Laboratories Metals Occupational Health Safety
• Keywords:
  Animal Studies Environmental Exposure Environmental Factors Laboratory Animals Toxic Effects Vanadium Compounds
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  275
• Issue:
  42
• NIOSHTIC Number:
  nn:20020703
• Citation:
  J Biol Chem 2000 Oct; 275(42):32516-32522
• Email:
  xas0@cdc.gov
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1) ; Vanadium (CAS RN 7440-62-2)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:58666ed76bddf7c7c50b72e42c32b980fa1a867a981834e668d2ee34102de42057a48c8fb48e44579dd3f9487e3cd7645d59ba851a1ab057deece6fe1d2b5213
• Download URL:
  https://stacks.cdc.gov/view/cdc/198381/cdc_198381_DS1.pdf
• File Type:
  [PDF - 229.50 KB ]