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Aldosterone breakthrough caused by chronic blockage of angiotensin II type-1 receptors in human adrenocortical cells : Involvement of bone morphogenetic protein-6 actions

Research Project

Project/Area Number 21790894
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionOkayama University

Principal Investigator

SUZUKI Jirou  Okayama University, 病院, 医員 (90452573)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアルドステロン / 骨形成蛋白 / シグナル伝達 / ステロイド合成
Research Abstract

We investigated whether aldosterone breakthrough occurs in human adrenocortical H295R cells in vitro. We recently reported that bone morphogenetic protein (BMP)-6 enhances Ang II-induced aldosterone production in human adrenocortical cells. Ang II stimulation was blocked by an ARB, candesartan. Interestingly, the candesartan effects on Ang II-induced aldosterone synthesis was attenuated in a course of candesartan treatment for 15 d. The impairment of candesartan effects on Ang II-induced aldosterone production was also observed in Ang II- or candesartanpretreated cells. BMP-6 enhancement of Ang II-induced ERK1/2 signaling was resistant to candesartan. The BMP-6-induced Smad1, -5, and -8 phosphorylation was augmented in the presence of Ang II and candesartan in the chronic phase. Chronic Ang II exposure decreased cellular expression levels of BMP-6 and its receptors mRNAs. Cotreatment with candesartan reversed the inhibitory effects of Ang II on the expression levels of these mRNAs. The breakthrough phenomenon was attenuated by neutralization of endogenous BMP-6 and activin receptor-like kinase-2. Collectively, these data suggest that changes in BMP-6 availability and response may be involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (11 results)

All 2010 2009

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (3 results)

  • [Journal Article] Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells.2010

    • Author(s)
      Otani H, Otsuka F, Inagaki K, Suzuki J, Makino H.
    • Journal Title

      Acta Medica Okayama 64

      Pages: 213-218

    • NAID

      120002383776

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional relationship between fibroblast growth factor-8 and bone morphogenetic proteins in regulating steroidogenesis by rat granulosa cells.2010

    • Author(s)
      Miyoshi T, Suzuki J, et. al.
    • Journal Title

      Molecular and cellular endocrinology. 325

      Pages: 84-92

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of bone morphogenetic protein (BMP) on adrenocorticotropin production by pituitary corticotrope cells2010

    • Author(s)
      Tsukamoto N, Suzuki J, et. al.
    • Journal Title

      Involvement of upregulation of BMP receptor signaling by somatostatin analogues. 151

      Pages: 1129-1141

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional relationship between fibroblast growth factor-8 and bone morphogenetic proteins in regulating steroidogenes is by rat granulosa cells.2010

    • Author(s)
      Miyoshi T, Suzuki J, et al
    • Journal Title

      Molecular and cellular endocrinology

      Volume: 325 Pages: 84-92

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells.2010

    • Author(s)
      Otani H, Suzuki J, et al
    • Journal Title

      Acta Medica Okayama

      Volume: 64 Pages: 213-218

    • NAID

      120002383776

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of bone morphogenetic protein (BMP) on adrenocorticotropin production by pituitary corticotrope cells : Involvement of upregulation of BMP receptor signaling by somatostatin analogues.2010

    • Author(s)
      Tsukamoto N, Suzuki J, et al.
    • Journal Title

      Endocrinology 151

      Pages: 11291141-11291141

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells.2009

    • Author(s)
      Goto J, Suzuki J, et. al.
    • Journal Title

      Am.J.Physiol.Endocrinology & Metabolism. 296

      Pages: 904-916

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells.2009

    • Author(s)
      Goto J, Suzuki J, et al.
    • Journal Title

      Am.J.Physiol.Endocrinology & Metabolism 296

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] A role of bone morphogenetic proteins in aldosterone-induced glomerular injury.2010

    • Author(s)
      Suzuki J, Otsuka F, et al.
    • Organizer
      Endo 2010
    • Year and Date
      2010-06-21
    • Related Report
      2010 Final Research Report
  • [Presentation] A role of bone morphogenetic proteins in aldosterone-induced glomerular injury2010

    • Author(s)
      Suzuki J, Otsuka F, et al.
    • Organizer
      Endo 2010
    • Place of Presentation
      米国(サンディエゴ)
    • Year and Date
      2010-06-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] アルドステロンによる腎糸球体障害におけるBone Morphogenetic Proteinの役割2009

    • Author(s)
      鈴木二郎, 他
    • Organizer
      第13回日本心血管内分泌代謝学会学術総会
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report 2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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