Abstract | BACKGROUND AND AIMS: Portal hypertensive (PHT) gastropathy results in an increased susceptibility to damage. Adaptive cytoprotection against ethanol-induced damage is impaired in the gastric mucosa of rats with portal hypertension. Excessive nitric oxide (NO) production occurs in portal hypertension and is mediated in part via heat-shock protein (Hsp)90 production. The aim of this study was to investigate the relation between adaptive cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT rats. METHODS:
Portal hypertension was induced in rats by staged portal vein occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the injury index of the gastric mucosa with or without pretreatment with 10% ethanol. Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction, and expression of Hsp90 protein was evaluated by western blotting. The effect of Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin. RESULTS: Gastric Hsp90 mRNA expression in PHT rats was significantly less than that in sham-operated (SO) controls. However, after 10% ethanol pretreatment, Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls. In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was significantly greater than that without the pretreatment. However, the pretreatment had no effect on the injury index compared to SO rats. Administration of geldanamycin prior to 10% ethanol pretreatment significantly decreased the injury index in response to 70% ethanol in the PHT rats. CONCLUSIONS: These results show that 10% ethanol pretreatment markedly increases gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may contribute impaired adaptive cytoprotection.
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Authors | Masayuki Tominaga, Masayuki Ohta, Seiichiro Kai, Kentaro Iwaki, Kohei Shibata, Seigo Kitano |
Journal | Journal of gastroenterology and hepatology
(J Gastroenterol Hepatol)
Vol. 24
Issue 6
Pg. 1136-41
(Jun 2009)
ISSN: 1440-1746 [Electronic] Australia |
PMID | 19383083
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Diterpenes
- HSP90 Heat-Shock Proteins
- Ethanol
- geranylgeranylacetone
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Topics |
- Animals
- Blotting, Western
- Cytoprotection
(drug effects)
- Diterpenes
(toxicity)
- Ethanol
(toxicity)
- Gastric Mucosa
(drug effects, metabolism)
- HSP90 Heat-Shock Proteins
(metabolism)
- Hypertension, Portal
(metabolism)
- Male
- Rats
- Rats, Sprague-Dawley
- Reverse Transcriptase Polymerase Chain Reaction
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