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

• Published in: Life sciences (1973) Vol. 91; no. 13-14; pp. 572 - 577
• Main Authors: Sakai, Satoshi, Kimura, Taizo, Wang, Zheng, Shimojo, Nobutake, Maruyama, Hidekazu, Homma, Satoshi, Kuga, Keisuke, Yamaguchi, Iwao, Aonuma, Kazutaka, Miyauchi, Takashi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.10.2012
• Subjects: Animals; Animals, Newborn; Atrial Natriuretic Factor - genetics; Cardiac hypertrophy; Cardiomegaly - pathology; cardiomyocytes; CTD phosphatase; DNA-directed RNA polymerase; Endothelin-1; Endothelin-1 - metabolism; FCP1; Gene Expression Regulation; genes; genetic markers; Humans; hypertrophy; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Myosin Heavy Chains - genetics; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Rats; Rats, Sprague-Dawley; RNA; RNA - biosynthesis; RNA polymerase II; RNA Polymerase II - metabolism; surface area; Transcription Factor TFIIH - metabolism; transcription factors; Up-Regulation; Cardiac hypertrophy; CTD phosphatase; FCP1; RNA polymerase II; Endothelin-1
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2012.04.034

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). 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. 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 [3H]-uridine incorporation showed that 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, the ET-1-induced increase in molecular markers of cardiac hypertrophy, expression of ANP and β-MHC gene, was suppressed by FCP1 and was not inhibited by dnFCP1. ET-1-induced cardiac hypertrophy and CTD phosphorylation level are functionally regulated by FCP1. These findings suggest that FCP1 plays an important role in ET-1-induced cardiac hypertrophy via controlling phosphorylation level of the RNAPII CTD.