Induction of a 72-kDa heat shock protein and cytoprotection against thioacetamide-induced liver injury in rats.
Heat shock proteins are ubiquitous intracellular proteins induced by various physiological stress-related events. A 72-kDa heat shock protein (HSP72) has been reported to be an endogenous cytoprotectant in variety of cells in vitro. In order to study the cytoprotective function of HSP72 in the liver, the effect of preinduction of HSP72 in rat liver by systemic hyperthermia on thioacetamide-induced hepatic injury was investigated in this study. Expression of HSP72 in the liver was investigated by immunoblot and densitometric analysis. Rats were injected with thioacetamide (100 mg/kg, subcutaneously) with or without preinduction of HSP72 by hyperthermia. Serum AST and ALT concentrations were measured before and after thioacetamide injection in both group. Histologic alteration of the liver was evaluated also. Systemic hyperthermia (42.5 degrees C, 20 min) significantly induced HSP72 in the liver. Thioacetamide-induced hepatic injury was clearly prevented by preinduction of HSP72 by hyperthermia. Prevention of hepatocyte damage was more clear in the area around central veins where HSP72 induction was apparent. Our findings might suggest that HSP72 has an important function in the liver with respect to cytoprotection. These results might be important for understanding the mechanism of "adaptive cytoprotection" in the liver mediated by the function of heat shock proteins as "molecular chaperons" as reported in vitro.
Fujimori
S
S
First Department of Internal Medicine, Akita University School of Medicine, Japan.
Otaka
M
M
Otani
S
S
Jin
M
M
Okuyama
A
A
Itoh
S
S
Iwabuchi
A
A
Sasahara
H
H
Itoh
H
H
Tashima
Y
Y
Komatsu
M
M
Masamune
O
O
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006979:Hyperthermia, Induced; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase