Role of heme oxygenase-1 in hydrogen peroxide-induced VEGF synthesis: effect of HO-1 knockout

Biochem Biophys Res Commun. 2005 Jan 21;326(3):670-6. doi: 10.1016/j.bbrc.2004.11.083.

Abstract

Hydrogen peroxide is an important mediator of intracellular signaling, which potently enhances the expression of heme oxygenase-1 (HO-1) and upregulates synthesis of vascular endothelial growth factor (VEGF). The purpose of the present study was to explore the involvement of HO-1 in regulation of H(2)O(2)-mediated induction of VEGF synthesis. We provide genetic evidence that basal and H(2)O(2)-induced VEGF synthesis is partially dependent on HO-1. Inhibition of HO-1 activity by tin protoporphyrin (SnPPIX) resulted in downregulation of VEGF synthesis in murine fibroblasts and human keratinocytes. The relationship between HO-1 and VEGF was corroborated by using cells derived from HO-1 knockout mice, which demonstrated lower basal and H(2)O(2)-induced production of VEGF. Additionally, knock out of HO-1 gene impaired induction of VEGF by hemin, lysophosphatidylcholine, and prostaglandin-J(2). Our results provide confirmation for the involvement of HO-1 in regulation of angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / metabolism
  • Endothelial Cells / metabolism
  • Gene Expression Regulation / physiology
  • Heme Oxygenase (Decyclizing) / deficiency
  • Heme Oxygenase (Decyclizing) / genetics*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Hydrogen Peroxide / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Membrane Proteins
  • Vascular Endothelial Growth Factor A
  • Hydrogen Peroxide
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse