c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model.
Ischemia/reperfusion injuries are a major problem in liver resections and transplantations. Tumor necrosis factor-alpha has been widely investigated as a key mediator in the mechanism of ischemia/reperfusion injury. Upstream signal transduction mechanisms for tumor necrosis factor-alpha have not been well documented. Therefore, we assessed c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model. Male Wistar rats were subjected to 30 minutes of ischemia followed by reperfusion. Hepatic enzymes, histological examinations, microfluorographs, and tumor necrosis factor-alpha protein production (in the serum and liver tissue) were analyzed during the course of reperfusion. c-Jun N-terminal kinase activity was measured by a radioisotope kinase assay. Ischemia/reperfusion injuries were characterized by an elevation in hepatic enzyme, the histological degeneration of hepatocytes, and an increase in the number of nonviable cells. Moreover, increased endothelial-adherent leukocytes and tumor necrosis factor-alpha protein production were also observed. c-Jun N-terminal kinase activity at 60 minutes after reperfusion was 12.4 times higher than the pre-ischemia level. These results suggest that c-Jun N-terminal kinase may play some role in the mechanism of ischemia/reperfusion injuries.
Shinoda
Masahiro
M
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Shimazu
Motohide
M
Matsuda
Satoshi
S
Wakabayashi
Go
G
Tanabe
Minoru
M
Hoshino
Ken
K
Kamei
Shusaku
S
Koyasu
Shigeo
S
Kitajima
Masaki
M
D000818:Animals; D004396:Coloring Agents; D004789:Enzyme Activation; D005452:Fluoresceins; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000201:enzymology* / Q000293:injuries*; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D023421:Models, Animal; D011419:Propidium; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004396:Coloring Agents; D005452:Fluoresceins; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; C084577:5-carboxyfluorescein diacetate; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases