Hydrogen peroxide induces midzonal heat shock protein 72 and apoptosis in sinusoidal endothelial cells of hypoxic rat liver.
OBJECTIVE
To investigate the heat shock protein (HSP) 72 expression and apoptosis induced by hydrogen peroxide in hypoxic rat liver.


METHODS
Prospective control study using the isolated rat liver.


METHODS
Animal research facility.


METHODS
Fasted, pathogen-free specific, male Sprague-Dawley rats.


METHODS
A low-flow hypoxia model was made by reducing an afferent pressure from 10 to 2.5 cm H2O, and by perfusing the isolated rat liver for 2 hrs.


RESULTS
We investigated the hydrogen peroxide production by using the 2'-7' dichlorofluorescein image, the induction of HSP 72 by using immunohistochemistry, and apoptosis by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method in the low flow hypoxic rat liver. In low-flow hypoxia, hydrogen peroxide production, HSP 72 expression, and apoptosis were induced in the midzone of rat liver. Prevalence of HSP 72 expression was higher in the sinusoidal endothelial cells (SEC) than in the hepatocytes. All apoptotic cells were SEC with expression of HSP 72. Hydrogen peroxide was derived from hepatocytes. Pretreatment with the specific xanthine oxidase inhibitor, sodium(-)-8-(3-methoxy-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate significantly attenuated hydrogen peroxide production, HSP 72 expression, and apoptosis of SEC in the midzone.


CONCLUSIONS
Xanthine oxidase-dependent hydrogen peroxide induces midzonal and SEC-dominant HSP 72 expression and apoptosis in hypoxic rat liver.
Motoyama
S
S
Second Department of Surgery, Akita University School of Medicine, Akita City, Japan.
Saito
S
S
Alojado
M E
ME
Itoh
H
H
Kitamura
M
M
Suzuki
H
H
Saito
R
R
Momiyama
H
H
Nakae
H
H
Ogawa
J
J
Inaba
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D000860:Hypoxia / Q000473:pathology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase