Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cattle
  • Cell Line
  • Cells, Cultured
  • Cyclic GMP
  • Endothelium, Vascular
  • Enzyme Activation
  • Gene Expression
  • Guanylate Cyclase
  • Heme Oxygenase-1
  • Humans
  • Iron
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinases
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases

MeSH Major

  • Apoptosis
  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)

abstract

  • Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-alpha. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO.

publication date

  • October 2, 2000

has subject area

  • Animals
  • Apoptosis
  • Carbon Monoxide
  • Cattle
  • Cell Line
  • Cells, Cultured
  • Cyclic GMP
  • Endothelium, Vascular
  • Enzyme Activation
  • Gene Expression
  • Guanylate Cyclase
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • Iron
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinases
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2193315

PubMed ID

  • 11015442

Additional Document Info

start page

  • 1015

end page

  • 1026

volume

  • 192

number

  • 7