FEBS Letters
Volume 583, Issue 18 , Pages 2997-3003, 17 September 2009

Inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced hypertrophic responses in rat neonatal cardiomyocytes: Involvement of the RhoA/Rho kinase pathway

Edited by Lukas Huber

  • Yang Ye

      Affiliations

    • Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qing-Chun Road, Hangzhou 310003, PR China
    • ,
  • Shen-Jiang Hu

      Affiliations

    • Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qing-Chun Road, Hangzhou 310003, PR China
    • E-Institute of Shanghai Universities, Division of Nitric Oxide and Inflammatory Medicine, PR China
    • Corresponding Author InformationCorresponding author. Address: Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qing-Chun Road, Hangzhou 310003, PR China. Fax: +86 571 87236628.
    • ,
  • Liang Li

      Affiliations

    • Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qing-Chun Road, Hangzhou 310003, PR China

Received 19 May 2009; received in revised form 22 July 2009; accepted 22 August 2009. published online 28 August 2009.

Abstract 

The RhoA/Rho-kinase (ROCK) pathway is involved in angiotensin (Ang) II-induced cardiac hypertrophy. However, it is still unclear whether inhibition of farnesylpyrophosphate (FPP) synthase can attenuate Ang II-induced hypertrophic responses, and whether it involves the RhoA/ROCK pathway. The anti-hypertrophic effects of inhibition of FPP synthase with alendronate in Ang II-cultured neonatal cardiomyocytes were partially reversed by geranylgeranyol (GGOH) and were mimicked by GGTI-286, a geranylgeranyl transferase-I inhibitor, C3 exoenzyme, an inhibitor of Rho, or Y-27632, an inhibitor of ROCK. Pull-down assay showed alendronate reduced-active RhoA by Ang II was also partially antagonized by GGOH. This study revealed that the inhibition of FPP synthase by alendronate reduces RhoA activation by diminishing geranylgeranylation which prevents Ang II-induced hypertrophic responses in neonatal cardiomyocytes.

Structured summary

MINT-7260047: Rhotekin-RBD (uniprotkb:Q9BST9) physically interacts (MI:0915) with Rhoa (uniprotkb:P61589) by pull down (MI:0096)

Keywords: Farnesylpyrophosphate synthase, Angiotensin II, Cardiomyocytes, RhoA, Geranylgeranylation

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PII: S0014-5793(09)00666-8

doi:10.1016/j.febslet.2009.08.034

FEBS Letters
Volume 583, Issue 18 , Pages 2997-3003, 17 September 2009

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