| Project/Area Number |
08044243
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | University of Tsukuba |
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Principal Investigator |
BANNAI Shiro University of Tsukuba Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (70019579)
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| Co-Investigator(Kenkyū-buntansha) |
ジョバンニ E・マン ロンドン大学, キングスカレッジ, 準教授
SATO Hideyo University of Tsukuba Institute of Basic Medical Sciences, Lecturer, 基礎医学系, 講師 (60235380)
ISHII Tetsuro University of Tsukuba Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 助教授 (20111370)
MANN Giovanni E King'S College, University of London, Reader
ジョバンニ E.マン ロンドン大学, キングスカレッジ, 準教授
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| Project Period (FY) |
1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | pancreas / pancreatitis / stress proteins / oxidative stress / glutathione / heme oxygenase |
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| Research Abstract |
The oxidative stress-inducible proteins are thought to function as one of the anti-oxidant systems in the cells. In this study, we have investigatad oxidative stress-inducible proteins, heme oxygenase (HO) and MSP23 as an oxidative stress-inducible protein found by us.
1. To investigate expression of HO in acute pancreatitis, pancreatitis was induced in rats by adminstering caerulein, a decapeptide cholecystokinin analogue, intraperitoneally. Inducible form HO-1 expression was not detected in the pancreas 1h after treatment of rats with caerulein, although interstitial oedema was observed in caerulein-treated rats. HO-1 was expressed selectively in pancreatic tissue 12-24 h after treatment of rats with caerulein, whereas expression of the constitutive form HO-2 and MSP23 remained unchanged.
2. In murine islet (BETATC3) and rat acinar (AR42J) pancreatic cell lines, oxidative stress such as hydrogen peroxide, methyl viologen, cadmium chloride, and diethylmaleate enhanced HO-1 expression in a dose-and time-dependent manner without altering expression of HO-2 and MSP23.
3. The sensitivity of BETATC3 to oxidative stress was different from that of AR42J cells. Therefore, we investigated the intracellular glutathione levels in these cells. The glutathione level in AR42J cells was significantly higher than that in BETATC3 cells. It was demonstrated that the higher level of glutathione in AR42J cells reflected the higher transport activity of cystine, which is a rate-limiting precursor amino acid for glutathione synthesis.
From these results, it was suggested that oxidative stress-inducible proteins play an important role in acute pancreatitis. The relationship between these proteins and diabetes deserves further exploration.
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