Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Western
  • Carrier Proteins
  • Caspase 8
  • Caspases
  • Cell Death
  • Cells, Cultured
  • Down-Regulation
  • Enzyme Activation
  • Enzyme Inhibitors
  • Lung
  • Mice
  • Mitochondria
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Protein Transport
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Time Factors
  • Up-Regulation
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • p38 Mitogen-Activated Protein Kinases

MeSH Major

  • Apoptosis
  • Endothelial Cells
  • Hepatocyte Growth Factor
  • Hypoxia
  • Oxygen

abstract

  • Hypoxia/reoxygenation causes cellular injury and death associated with a number of pathophysiological conditions, including myocardial ischemia/reperfusion injury and stroke. The cell death pathways induced by hypoxia/reoxygenation and their underlying regulatory mechanisms remain poorly understood. Recent studies have shown that hypoxia/reoxygenation can induce Bax translocation and cytochrome c release. Using murine lung endothelial cells as a model, we found that the induction of apoptosis by hypoxia/reoxygenation involved the activation of both Bax-dependent and death receptor-mediated pathways. We demonstrated the activation of the death-inducing signal complex and Bid pathway after hypoxia/reoxygenation. Hepatocyte growth factor markedly inhibited hypoxia/reoxygenation-induced endothelial cell apoptosis. The cytoprotection afforded by hepatocyte growth factor was mediated in part by the stimulation of FLICE-like inhibiting protein expression, the attenuation of death-inducing signal complex formation, and the inhibition of Bid and Bax activation. Hepatocyte growth factor also prevented cell injury and death by increasing the expression of the antiapoptotic Bcl-XL protein. The inhibition of Bid/Bax-induced cell death by hepatocyte growth factor primarily involved p38 MAPK and in part Akt-dependent pathways but not ERK1/ERK2.

publication date

  • February 13, 2004

has subject area

  • Animals
  • Apoptosis
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Western
  • Carrier Proteins
  • Caspase 8
  • Caspases
  • Cell Death
  • Cells, Cultured
  • Down-Regulation
  • Endothelial Cells
  • Enzyme Activation
  • Enzyme Inhibitors
  • Hepatocyte Growth Factor
  • Hypoxia
  • Lung
  • Mice
  • Mitochondria
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Oxygen
  • Protein Transport
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Time Factors
  • Up-Regulation
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • p38 Mitogen-Activated Protein Kinases

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M309271200

PubMed ID

  • 14625309

Additional Document Info

start page

  • 5237

end page

  • 5243

volume

  • 279

number

  • 7