Vanadate Induces Cell Growth Arrest Through MAPKs and Reactive Oxygen Species

Details

• Personal Author:
  Chen F ; Chuang C ; Leonard, Stephen S. ; Qian Y ; Shi X ; Zhang Z
• Description:
  Cell growth arrest is an important mechanism in maintaining genomic stability and integrity in response to environmental stress. Using human lung epithelial cell line, A649, the present study investigates the role of reactive oxygen species (R08) and ERK and p38 protein kinase in vanadate-induced cell growth arrest. Exposure of the cells to vanadate led to cell growth arrest at G2/M phase and caused up-regulation of p21 and phpho-cdc2 and degradation of cdc25C. Vanadate activated phosphorylation of ERK and p38. PD98059 and SB202190 not only decreased phosphorylation of ERK and p38 activated by vanadate, also inhibited vanadate-induced G2/M arrest, up-regulation of p21 an4 cdc2 and degradation of cdc25C. Cellular reduction of vanadate generated hydroxyl radical as determined by electron spin resonance (ESR) and superoxide radical and hydrogen peroxide as determined by flow cytometry and confocal microscopy in combination with specific antioxidant enzymes, Buperoxide dismutase and catalase. Among ROS generated by cellular reduction of vanadate, both hydroxyl radical and hydrogen peroxide play an important role in vanadate-induced activation of ERK and p38, up-regulation of p21 and phospho-cdc2, and degradation of cdc25C. These results suggest that cellular reduction of vandate generates hydroxyl radical and hydrogen peroxide via superaxide anion as an intermediate. ROS activate ERK and p38, which in turn up-regulate, p21 and cdc2 and cause degradation of cdc25C leading to cell growth arrest at G2/M phase. ROS affect different MAPK family members and cell growth regulatory proteins with different potencies. [Description provided by NIOSH]
• Subjects:
  Genetics Occupational Health Safety Vanadium Compounds
• Keywords:
  Cell-growth Cell-morphology Genetic-disorders Genotoxic-effects Humans Vanadium-compounds
• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  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:
  31
• NIOSHTIC Number:
  nn:20032281
• Citation:
  Free Radic Biol Med 2001 Nov; 31(Suppl 1):S108
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1) ; Sodium vanadium oxide (Na3VO4) (CAS RN 13721-39-6)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  False
• Source Full Name:
  Free Radical Biology and Medicine
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85e2111524ce10d9ed4222953b05b35f25a496cbffd58f3820d497b8545550f049468e7d6f03003e76a8ab45d7a4e984f1cfa9e2139fd893c577997e61cd2f44
• Download URL:
  https://stacks.cdc.gov/view/cdc/186309/cdc_186309_DS1.pdf
• File Type:
  [PDF - 117.95 KB ]