| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Although sterylglucosides are widespread membrane lipids in plants, algae, fungi, and slime molds, their physiological functions remain to be clarified. In this study, we demonstrated the possible roles of cholesterylglucoside (CG) as a mediator molecule in cellular stress responses.
1. Induction of CG in mammalian cell lines, tissues and organs: Specific induction of CG by heat shock in human cultured fibroblasts, TIG-3 cells, was observed. In addition, it was shown that CG is accumulated in various organs in rat by either oxidative stress or cold-restraint stress. Apparent increases in the level of CG in lung, liver, kidney and small intestine by oxidative stress were observed, whereas cold-restraint stress induced the organ-specific accumulation of CG in stomach and kidney.
2. Protective effect of CG against stress-induced gastric ulcer in rat: When CG was orally administered to rat 30 min prior to the stress application, the formation of gastric ulcer was markedly suppressed as compared to control. Orally administered CG caused the rapid activation of HSF1 and the subsequent expression of HSP70 in gastric mucous cells. These findings suggest that CG may act as a lipid mediator in an early stage of the stress signal transduction system.
3. CG synthetic enzyme: We have characterized the enzyme responsible for the CG synthesis. The enzyme is a membrane-bound glucosyltransferase, which uses UDP-glucose and cholesterol as substrate. Cloning of the structural gene for the enzyme is now in progress.
These studies suggest the possibility that CGs are effective cytoprotective agents being enable to use for medical treatment of gastric ulcer and many other stress-inducible diseases via HSP induction.
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