2004 Fiscal Year Final Research Report Summary
Endothelial cell ER stress and Ca^<2+> signaling pathway
| Project/Area Number |
14570652
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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 |
Circulatory organs internal medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
WATANABE Hirosi Hamamatsu University School of Medicine, Clinical Pharmacology and Ther apeutics, Professor, 医学部, 教授 (50262803)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Hideki Hamamatsu University School of Medicine, Internal Medicine III, Assistant Prof., 医学部, 助手 (80314029)
SATOH Hirosi Hamamatsu University School of Medicine, Internal Medicine III, Assistant Prof., 医学部附属病院, 助手 (30293632)
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| Project Period (FY) |
2002 – 2004
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| Keywords | apoptosis / endothelial cell / calcium / ER stress / caspase |
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| Research Abstract |
Apoptosis of endothelial cells (ECs) is now regarded to be an initial step inducing atherosclerosis. Recent studies have reported that the depletion of endoplasmic reticulum (ER) Ca^<2+> stores plays an important role in apoptosis. Caspase-12 is a key signal to lead ER stress-induced apoptosis. However, it is not known whether the depletion of ER Ca^<2+> is linked to caspase-12 signaling in ECs. Here we have investigated the interaction of Ca^<2+> signaling and caspase-12 cleavage in apoptosis of cultured porcine aortic ECs. Cytosolic Ca^<2+> concentration ([Ca^<2+>]i) was measured using fura-2/AM. Apoptosis was assessed by DNA ladder formation, and cleavage of caspase-12 by Western blotting. Thapsigargin (6μM), an inhibitor of the ER-associated Ca^<2+>-ATPase, increased [Ca^<2+>]i (F340/F380 ratio 0.717±0.137 to 6.133±0.710 : p<0.001) and induced persistent ER calcium depletion, cleavage of caspase-12 and apoptosis. Bradykinin (10 nM) increased [Ca^<2+>]i (F340/F380 ratio 0.717±0.053 to 6.133±0.528 : p<0.001) but induced neither cleavage of caspase-12 nor apoptosis. However, when ECs were treated with BAPTA/AM (100μM), BK caused the Ca^<2+> depletion of ER and apoptosis without the cleavage of caspase-12. Moreover non-selective caspase inhibitor, zVAD-fmk (100μM), inhibited apoptosis and cleavage of caspase-12 in TG-stimulated ECs, and calpain inhibitor, MDL 28170 (120μM), inhibited cleavage of caspase-12 but not inhibited apoptosis. These results suggested that the increase of [Ca^<2+>]i did not play an important role in inducing apoptosis in ECs, and ER Ca^<2+> depletion induced apoptosis, which is independent from caspase-12 linked signaling pathway.
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Research Products
(6 results)
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[Journal Article] Nitric oxide : inhibitory effects on endothelial cell calcium signaling, prostaglandin I_2 production and nitric oxide synthase expression.2004
Author(s)
Takeuchi K, Watanabe H, Tran QK, Ozeki M, Sumi D, Hayashi T, Iguchi A, Ignarro LJ, Ohashi K, Hayashi H
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Journal Title
Cardiovascular Research 62
Pages: 194-201
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Nitric oxide : inhibitory effects on endothelial cell calcium signaling, prostaglandin I_2 production and nitric oxide synthase expression2004
Author(s)
Takeuchi K, Watanabe H, Tran QK, Ozeki M, Sumi D, Hayashi T, Iguchi A, Ignarro LJ, Ohashi K, Hayashi H
-
Journal Title
Cardiovascular Research 62
Pages: 194-201
Description
「研究成果報告書概要(欧文)」より
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