HCMV infection attenuates hydrogen peroxide induced endothelial apoptosis-- involvement of ERK pathway

FEBS Lett. 2006 May 15;580(11):2779-87. doi: 10.1016/j.febslet.2006.04.041. Epub 2006 Apr 25.

Abstract

Human cytomegalovirus (HCMV) exerts anti-apoptotic effect during early stage of infection, which provides HCMV time for propagation. We investigated pathways mediating the resistance to H(2)O(2)-induced cell death - a self-defense mechanism to remove infected cells. We found that human aortic endothelial cells (HAECs) infected with VHL/E strain of HCMV during first 3 days were resistant to H(2)O(2) (0-2 mM) induced apoptosis. This anti-apoptotic effect may be mediated by the upregulation of Bcl-2, an anti-apoptotic protein through the activation pro-survival pathway extracellular signal regulated kinase (ERK). Through this mechanism, HCMV is able to propagate and causes endothelial dysfunction, hence vascular disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Cytomegalovirus / physiology*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelial Cells / virology*
  • Enzyme Activation / drug effects
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Intracellular Membranes / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Membrane Potentials / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • Up-Regulation

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Hydrogen Peroxide
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • CASP3 protein, human
  • Caspase 3
  • Caspases