Hypoxia-reoxygenation differentially stimulates stress-activated protein kinases in primary-cultured rat hepatocytes.
Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 microM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.
Crenesse
D
D
Laboratoire de Physiologie, Faculté de Médecine, Université de Nice-Sophia Antipolis, Nice, France.
Schmid-Alliana
A
A
Hornoy
J
J
Rossi
B
B
Gugenheim
J
J
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases