title: Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. ssakai@md.tsukuba.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakai
authors.forename: Taizo
authors.initials: T
authors.lastname: Kimura
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Nobutake
authors.initials: N
authors.lastname: Shimojo
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Maruyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Homma
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuga
authors.forename: Iwao
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000473:pathology*; D019332:Endothelin-1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D012313:RNA / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; C000594638:MYH7 protein, rat; D051758:Transcription Factor TFIIH; D012313:RNA; D009320:Atrial Natriuretic Factor; D012319:RNA Polymerase II; D010749:Phosphoprotein Phosphatases; C116022:carboxy-terminal domain phosphatase; D018995:Myosin Heavy Chains