Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells.

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.
Authors	Xue Wang, Yushen Zhou, Hong Pyo Kim, Ruiping Song, Reza Zarnegar, Stefan W Ryter, Augustine M K Choi
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 7 Pg. 5237-43 (Feb 13 2004) ISSN: 0021-9258 [Print] United States
PMID	14625309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	BH3 Interacting Domain Death Agonist Protein Bax protein, mouse Bcl2l1 protein, mouse Bid protein, mouse Carrier Proteins Enzyme Inhibitors Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 bcl-2-Associated X Protein bcl-X Protein Hepatocyte Growth Factor Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases Casp8 protein, mouse Caspase 8 Caspases Oxygen
Topics	Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Blotting, Western Carrier Proteins (metabolism) Caspase 8 Caspases (metabolism) Cell Death Cells, Cultured Down-Regulation Endothelial Cells (cytology, pathology) Enzyme Activation Enzyme Inhibitors (pharmacology) Hepatocyte Growth Factor (metabolism) Hypoxia Lung (cytology) Mice Mitochondria (metabolism) Mitogen-Activated Protein Kinase 1 (metabolism) Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases (metabolism) Oxygen (metabolism) Protein Transport Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-bcl-2 (metabolism) Time Factors Up-Regulation bcl-2-Associated X Protein bcl-X Protein p38 Mitogen-Activated Protein Kinases

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!