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

Authors: Sakai, S  Kimura, T  Wang, Z  Shimojo, N  Maruyama, H  Homma, S  Kuga, K  Yamaguchi, I  Aonuma, K  Miyauchi, T 
Citation: Sakai S, etal., Life Sci. 2012 Oct 15;91(13-14):572-7. doi: 10.1016/j.lfs.2012.04.034. Epub 2012 Apr 30.
Pubmed: (View Article at PubMed) PMID:22569295
DOI: Full-text: DOI:10.1016/j.lfs.2012.04.034

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 [(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 beta-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.

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CRRD Object Information
CRRD ID: 9686371
Created: 2015-02-04
Species: All species
Last Modified: 2015-02-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.