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Endothelial cell ER stress and Ca^<2+> signaling pathway

Research Project

Project/Area Number 14570652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

WATANABE Hirosi  Hamamatsu University School of Medicine, Clinical Pharmacology and Ther apeutics, Professor, 医学部, 教授 (50262803)

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)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsapoptosis / endothelial cell / calcium / ER stress / caspase / Akt / PI3キナーゼ
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.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All 2005 2004 2003

All Journal Article (8 results)

  • [Journal Article] Modification of sarcoplasmic reticulum (SR) Ca^<2+> release by FK506 induces defective excitationcontraction coupling only when SR Ca^<2+> recycling is disturbed2005

    • Author(s)
      Yoshihara S, Satoh H, Saotome M, Katoh H, Terada H, Watanabe H, Hayashi H
    • Journal Title

      Can.J.Physiol.Pharmacol. 83

      Pages: 357-366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Akt and Ca^<2+> signaling in endothelial cells.2004

    • Author(s)
      Ozeki M, Watanabe H, Luo JH, Nakano T, Takeuchi K, Kureishi Y, Ito M, Nakano T, Ohashi K, Hayashi H.
    • Journal Title

      Molecular and Cellular Biochemistry 259

      Pages: 169-176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Journal Title

      Cardiovascular Research 62

      Pages: 194-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Akt and Ca^<2+> signaling in endothelial cells2004

    • Author(s)
      Ozeki M, Watanabe H, Luo JH, Nakano T, Takeuchi K, Kureishi Y, Ito M, Nakano T, Ohashi K, Hayashi H.
    • Journal Title

      Molecular and Cellular Biochemistry 259

      Pages: 169-176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Akt and Ca^<2+> signaling in endothelial cells.2004

    • Author(s)
      Ozeki M, Watanabe H, Luo JH, Nakan o T, Takeuchi K, Kureishi Y, Ito M, Na kano T, Ohashi K, Hayashi H.
    • Journal Title

      MOLECULAR AND CELLULAR BIOCHEMISTRY 259

      Pages: 169-176

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nitric oxide : inhibitory effects on endothelial cell calcium signaling, prostaglandin 12 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
    • Journal Title

      CARDIOVASCULAR RESEARCH 62

      Pages: 194-201

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of cytochrome P450 inhibitors on agonistinduced Ca^<2+> responses and production of NO and PGI_2 in vascular endothelial cells2003

    • Author(s)
      Takeuchi K, Watanabe H, Tran QK, Ozeki M, Uehara A, Katoh H, Satoh H, Terada H, Ohashi K, Hayashi H
    • Journal Title

      Molecular and Cellular Biochemistry 248

      Pages: 129-134

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2002-04-01   Modified: 2016-04-21  

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