Arsenic Induced an Increase in Endothelial Cell Permeability: Involvement of Cytoskeleton Signaling

Details

• Personal Author:
  Castranova, Vincent ; Qian Y ; Shi X ; Ward R
• Description:
  Although it has been shown that human exposure to arsenic is related to an increase in inflammation, cardiovascular diseases, and cancers, the molecular mechanisms of its action remains to be elucidated. In this study, we demonstrated that exposure to arsenic caused an increase in cell permeability in human microvascular endothelial cells (HMEC), which is correlated with the remodeling of actin, microtubule cytoskeleton, and the activation of Erk1/2 signaling by the production of reactive oxygen species (ROS). Inhibition of Erk1/2 activities, blockage of actin filament remodeling, or removal of ROS partially suppressed the arsenic-induced permeability increase, indicating the involvement of cytoskeleton, Erk1/2, and ROS signaling pathways in arsenic-induced endothelial cell morphological changes. Furthermore, we found that arsenic treatment disrupted the localization of VE-cadherin at adherens junctions in HMEC and induced its translocation into the nucleus. Moreover, it was found that arsenic-induced VE-cadherin nuclear translocation was inhibited by treatments with ROS scavengers, and actin filament and microtubule inhibitors. Taken together, this study demonstrates that arsenic stimulation induces an increase in cell permeability in HMEC, which involves actin and microtubule cytoskeleton signaling. The results from this study may contribute to dissecting the molecular mechanisms involved in arsenic toxicity. [Description provided by NIOSH]
• Subjects:
  Cardiovascular Diseases Cardiovascular System Chemistry Hazardous Substances Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Cardiovascular-system-disorders Cell-morphology Cell-wall-permeability Chemical-properties Molecular-biology Skeletal-system-disorders Toxic-effects Toxins
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; 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:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033640
• Citation:
  Toxicologist 2008 Mar; 102(1):334
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:20e2714e3d181494c5aea823fce1ce9585c97eeea31247cb41cfd4fe0d772428c5b2d486f2772eb89e14c9499777b9a5723a762f27c90e9513685d26eb996750
• Download URL:
  https://stacks.cdc.gov/view/cdc/189126/cdc_189126_DS1.pdf
• File Type:
  [PDF - 7.65 MB ]