Arsenic Activates NADPH Oxidase Through CDC42 and Their Involvement in Actin Filament Remodeling and Cell Motility in Endothelial Cells

Details

• Personal Author:
  Castranova, Vincent ; Flynn DC ; Qian Y ; Shi X
• Description:
  Although arsenic is a human carcinogen, the molecular mechanisms of its action remain to be understood. By stimulating mouse endothelial cell lines (SVEC4-10) with 10 uM arsenic, we found that arsenic induced activation of NADPH oxidase as determined by the nitroblue tetrazolium test. Using confocal microscopy, the generation of O2 and H2O2 was observed to be increased in SVEC4-10 cells after exposure to arsenic. We also found that arsenic activated Small Rho GTPase CDC42. Disruption of CDC42 with a dominant negative CDC42 abolished arsenic-induced activation of NADPH oxidase and subsequent generation of O2 and H2O2 suggesting that CDC42 may mediate the effects of arsenic on NADPH oxidase. Furthermore, it was found that arsenic stimulation induced actin filament remodeling increased cell motility in SVEC4-10 cells. These changes were abrogated by either disruption of CDC42 or inhibition of NADPH oxidase, indicating that the cell signaling changes induced by arsenic are relevant to these cellular functions. Taken together, the data imply that arsenic may promote motility-dependent metastasis of cancer cells through CDC42, NADPH oxidase and reactive oxygen species. [Description provided by NIOSH]
• Subjects:
  Animals Arsenic Carcinogens Inorganic Chemicals Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Arsenic-compounds Cellular-function Exposure-levels Laboratory-animals Microscopy
• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  78
• NIOSHTIC Number:
  nn:20026829
• Citation:
  Toxicologist 2004 Mar; 78(S-1):337
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
• Supplement:
  S-1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0345ea61d1aa6b7420de37c0ca53ea3e39e108ad5193f8d228fa2a2a25533a3dc79d0b9d973179efbd9f1615751a412c10ea03358abedb6880e08845706acd51
• Download URL:
  https://stacks.cdc.gov/view/cdc/197389/cdc_197389_DS1.pdf
• File Type:
  [PDF - 56.49 KB ]