| Project/Area Number |
09670631
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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 |
Respiratory organ internal medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
YASUI Shuji Tokyo Women's Medical University First Department of Medicine Assistant Professor, 医学部, 講師 (30147392)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Atsushi Tokyo Women's Medical University First Department of Medicine Professor, 医学部, 教授 (60101820)
AOSHIBA Kazutetsu Tokyo Women's Medical University First Department of Medicine Instructor, 医学部, 助手 (60231776)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | thiol / oxidant / antioxidant / apoptosis / fibroblasts / p-38 MAPK / lung / 肺傷害 / p38-MAPK |
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| Research Abstract |
Thiol antioxidants are implicated in the protection of cells from oxidative injury. We studied the role of thiols in the regulation of apoptosis in cultured lung fibroblasts. Thiol depletion by culturing fibroblasts in cystine-free medium or with thiol-depleting agents induced oxidant accumulation and cell death by apoptosis. The cell death was prevented by the antioxidants ascorbic acid and catalase. Thiol depletion also induced leukotriene production and selective phosphorylation of p38-mitogen-activated protein kinase (MAPK). Leukotriene production and p38-MAPK phosphorylation were required for induction of apoptosis since thiol depletion-induced apoptosis was completely blocked by the 5-lipoxygenase inhibitor AA861, the leukotriene antagonists FPL55712 and ONO1078, and the p38-MAPK inhibitor SB203580. Leukotriene production was inhibited by ascorbic acid, AA861, and FPL55712. In an in vitro scratch wound model, repopulating fibroblasts at the wound margin, but not quiescent cells at the intact site, selectively underwent thiol depletion-induced apoptosis. Thus, thiol depletion induces apoptosis through an ordered pathway involving oxidant accumulation, leukotriene production, and p38-MAPK activation. Apoptosis of wound fibroblasts may be responsible for impaired wound healing in various organs including lung.
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