- 作者：Satoshi Sakai ; Taizo Kimura ; Zheng Wang ; Nobutake Shimojo ; Hidekazu Maruyama ; Satoshi Homma ; Keisuke Kuga ; Iwao Yamaguchi ; Kazutaka Aonuma ; Takashi Miyauchi
- 关键词：FCP1 ; CTD phosphatase ; Cardiac hypertrophy ; Endothelin-1 ; RNA polymerase II
- 刊名：Life Sciences
- 出版年：2012
- 出版时间：15 October, 2012
- 年：2012
- 卷：91
- 期：13-14
- 页码：572-577
- 全文大小：905 K
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 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 ¦Â-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 ET-1-induced cardiac hypertrophy via controlling phosphorylation level of the RNAPII CTD.