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

[摘要] Aims: Cardiac hypertrophy is associated with the increase of total amount of RNA, which is in accordance with RNA polymerase II (RNAPII) activation via C-terminal domain (CTD) phosphorylation of the largest subunit of RNAPII. It has been demonstrated that endothelin-1 (ET-1) phosphorylates CTD at the hypertrophic response in cardiomyocytes. However, it is unclear whether ET-1-induced hypertrophy is affected by the CTD phosphatase, transcription factor IIF-interacting CTD phosphatase1 (FCP1). Main methods: We analyzed whether ET-1-induced cardiomyocyte hypertrophy was affected by overexpression of FCP1 or dominant-negative form of FCP1 (dnFCP1) in neonatal rat cardiomyocytes. Key findings: The level of Er-1-induced RNAPII CTD phosphorylation was decreased by FCP1 overexpression, whereas it was sustained by dnFCP1. Global RNA synthesis evaluated by [H-3]-uridine incorporation showed that the Er-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, the ET-1-induced increase in molecular markers of cardiac hypertrophy, expression of ANP and 13-MHC gene, was suppressed by FCP1 and was not inhibited by dnFCP1. Significance: ET-1-induced cardiac hypertrophy and CTD phosphorylation level are functionally regulated by FCP1. These findings suggest that FCP1 plays an important role in Er-1-induced cardiac hypertrophy via controlling phosphorylation level of the RNAPII CTD. (c) 2012 Elsevier Inc. All rights reserved.

[发布日期] 2012-10-15

[效力级别]  Proceedings Paper

[关键词] FCP1;CTD phosphatase;Cardiac hypertrophy;Endothelin-1;RNA polymerase II