Rheb activates protein synthesis and growth in adult rat ventricular cardiomyocytes

Journal of Molecular and Cellular Cardiology
Yanni WangChristopher G Proud

Abstract

The mammalian target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis, growth and proliferation in mammalian cells, is implicated in the development of cardiac hypertrophy. Ras homolog enriched in brain (Rheb) positively regulates mTORC1. We have studied whether Rheb is sufficient to activate mTOR signaling and promote protein synthesis and cardiac hypertrophy in adult rat ventricular cardiomyocytes (ARVC). Rheb was overexpressed via an adenoviral vector in isolated ARVC. Overexpression of Rheb in ARVC activated mTORC1 signaling, several components of the translational machinery and stimulated protein synthesis. Our direct visualization approach to determine ARVC size revealed that overexpression of Rheb also induced cell growth and indeed did so to similar extent to the hypertrophic agent, phenylephrine (PE). Despite potent activation of mTORC1 signaling, overexpression of Rheb did not induce expression of the cardiac hypertrophic marker mRNAs for brain natriuretic peptide and atrial natriuretic factor, while PE treatment did markedly increase their expression. All the effects of Rheb were blocked by rapamycin, confirming their dependence on mTORC1 signaling. Our findings reveal that Rheb itself can activa...Continue Reading

References

Jun 25, 2002·Genes & Development·Diane C FingarJohn Blenis
Jan 28, 2003·Lancet·Rossella Fattori, Tommaso Piva
Apr 2, 2003·Circulation·Tetsuo ShioiSeigo Izumo
Apr 12, 2003·The American Journal of Medicine·David G Gardner
Aug 2, 2003·Clinical and Experimental Pharmacology & Physiology·R D HannanY Brandenburger
Nov 11, 2003·Trends in Biochemical Sciences·Brendan D Manning, Lewis C Cantley
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall
May 11, 2006·Current Heart Failure Reports·Risto Kerkela, Thomas Force
Aug 1, 2006·Journal of Hypertension·Xiao-Ming GaoXiao-Jun Du
Sep 14, 2006·Annual Review of Pharmacology and Toxicology·Chung-Han LeeKun-Liang Guan
Sep 23, 2006·Physiology·Xuemin Wang, Christopher G Proud
Oct 17, 2006·Oncogene·J B Easton, P J Houghton

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Citations

Jun 9, 2014·Human Molecular Genetics·Yukiko HasumiW Marston Linehan
Feb 16, 2011·Molecular and Cellular Biology·Susanna M I GoordenYpe Elgersma
Mar 21, 2013·Journal of Molecular and Cellular Cardiology·Ze ZhangChristopher G Proud
Feb 11, 2015·Cell Reports·Richa TyagiSrinivasa Subramaniam
Dec 26, 2018·Circulation Research·Erik A BlackwoodChristopher C Glembotski
Dec 22, 2012·Nature Reviews. Molecular Cell Biology·Marjorie MailletJeffery D Molkentin
Dec 17, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Brandon P H HuangChristopher G Proud
Feb 5, 2021·Journal of Cardiovascular Pharmacology·Chi ZhangJian Yang
Aug 5, 2021·Biological Research·Manuel Ramos-KuriElie R Chemaly

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