| Project/Area Number |
04454266
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University School of Medicine the 1st Department of Internal Medicine Professor, 医学部, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
SUEMATU Masakuni Kobe University School of Medicine the 1st Department of Internal Medicine Assis, 医学部・附属病院, 助手 (90240853)
KAWASHIMA Yasuhiro Kobe University School of Medicine The 1st Department of Internal Medicine Assis, 医学部, 助手 (10177678)
KAWAHARA Ysuhiro Kobe University School of Medicine The 1st Department of Internal Medicine, 医学部・附属病院, 講師 (80169755)
ISHIKAWA Yuichi Kobe University School of Medicine The Allied Medical Sciences Professor, 医療技術短期大学部, 教授 (90159707)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | vascular endothelial cells / endothelium-derived relaxing factor / low density lipoprotein / high density lipoprotein / nitric synthase / protein kinase C / lysophosphatidylcholine / intracellular calcium concentration |
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| Research Abstract |
(1) Effect of lipoproteins and lysolipids on endothelium-dependent relaxation
We have demonstrated that lysophosphatidylcholine (LPC) in oxidized low density lipoprotein (ox-LDL) inhibits the synthesis of EDRF/NO in endothelial cells. LPC and ox-LDL inhibit the intracellular signal transduction which links the receptor stimulation to biosynthesis of the second massenger in endothelial cells, leading to an endothelial defect in the generation at appropriate intracellular calcium signals nesessary for activation of NO synthase. HDL reverses the ox-LDL-induced impairment of endothelium-dependent relaxation by removing LPC from ox-LDL
(2) Regulation of endothelial NO synthase (NOS)
We have purified endothelial NOS from cultured bovine aortic endothelial cells (BAECs). Endothelial NOS was mainly regulated Ca^<2+>/calmodulin in the presence of NADPH,FAD and BH_4 as cofactors. NOS activity was enhanced approximately up to three fold by PC, LPC and phosphatidylethanolamice. NOS mRNA expression was investigated in BAECs. LPC or ox-LDL enhanced NOS mRNA expression.Interferon alpha/beta increased NOS mRNA expression, but TNF-alpha inhibited it.
(3) Regulation of inducible NOS (iNOS) mRNA expression in vascular smooth muscle cells. interferon gamma, TNF alpha and interleukin-1beta each markedly increased mRNA and protein levels of iNOS in parallel with the production of nitrite. TGF-beta significantly inhibited the increase in protein levels caused by these cytokines.
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