Endothelin-1­induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II

Article history:Received 21 November 2011Accepted 13 April 2012Keywords:FCP1CTD phosphataseCardiac hypertrophyEndothelin-1RNA polymerase II Aims: Cardiac hypertrophy is associated with the increase of total amount of RNA, which is in accordance withRNA polymerase II (RNAPII) activation via C-terminal domain (CTD) phosphorylation of the largest subunit ofRNAPII. It has been demonstrated that endothelin-1 (ET-1) phosphorylates CTD at the hypertrophic responseincardiomyocytes.However,itisunclearwhetherET-1-inducedhypertrophyisaffectedbytheCTDphosphatase,transcription factor IIF-interacting CTD phosphatase1 (FCP1).Mainmethods: We analyzed whether ET-1-induced cardiomyocyte hypertrophy was affected by overexpressionof FCP1 or dominant-negative form of FCP1 (dnFCP1) in neonatal rat cardiomyocytes.Key findings: The level of ET-1-induced RNAPII CTD phosphorylation was decreased by FCP1 overexpression,whereas it was sustained by dnFCP1. Global RNA synthesis evaluated by [ 3 H]-uridine incorporation showedthat the ET-1-induced increase in RNA synthesis was suppressed by FCP1 and was augmented by dnFCP1. ET-1-induced increase in cell surface area was suppressed by FCP1 and was preserved by dnFCP1. Furthermore, theET-1-induced increase in molecular markers of cardiac hypertrophy, expression of ANP and β-MHC gene, wassuppressed by FCP1 and was not inhibited by dnFCP1.Significance: ET-1-inducedcardiachypertrophyandCTDphosphorylationlevelarefunctionallyregulatedbyFCP1.These findings suggest that FCP1 plays an important role in ET-1-induced cardiac hypertrophy via controllingphosphorylation level of the RNAPII CTD.© 2012 Elsevier Inc. All rights reserved.