1997 Fiscal Year Final Research Report Summary
Signal transduction in hepatocytes-Long-term alcohol effects on small G-proteins
| Project/Area Number |
08670552
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
NOMURA Fumio University of Tsukuba, Institute of Clinical Medicine, Associate Professor, 臨床医学系, 助教授 (80164739)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAI Toshiaki University of Tsukuba, Institute of Clinical Medicine, Professor, 臨床医学系, 教授 (30049192)
NODA Masatoshi Chiba University, School of Medicine, Professor, 医学部, 教授 (60164703)
ISOBE Kazumasa University of Tsukuba, Institute of Clinical Medicine, Lecturer, 臨床医学系, 講師 (10151440)
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| Project Period (FY) |
1996 – 1997
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| Keywords | ADP-ribosylation / Alcohol / Phosphoglucomutase |
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| Research Abstract |
ADP-ribosylation is a post-translational protein modification which in turn alters several regulatory proteins in mammalian cells. We demonstrated that long-term alcohol intake enhanced the ADP-ribosylation of a 58kDa protein in rat liver plasma membranes. To assess the biological significance of this phenomenon, we partially purified the 58kDa acceptor protein from solubilized rat liver homogenates by two sequential preparative HPLCs. Microsequencing revealed that it was phosphoglucomutase (EC 5,4,2,2). This enzyme underwent negligible auto ADP-ribosylation, but the ADP-ribosylation was remarkably increased by adding rat liver plasma membrances. The extent of the increase was greater in alcohol-fed rats than in pair-fed controls, suggesting enhanced enzyme activities toward ADP-ribosylation of phosphoglucomutase after chronic alcohol consumption. Several important enzymes are ADP-ribosylated, after which their activities are modified. The results of this study showed that phosphoglucomutase is a novel substrate for ADP-ribosylation in the liver and that the ADP-ribosylation is increased after chronic alcohol consumption. In view of the variety of roles of phosphoglucomutase in the liver (carbohydrate metabolism and Ca^<2+>homeostasis), specific roles of this modification in terms of alcohol effects on hepatocytes may deserve further investigation.
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