Angiotensin II promotes poly(ADP-ribosyl)ation of c-Jun/c-Fos in cardiac fibroblasts

Dan Huang, Yan Wang, Chongzhe Yang, Yuhua Liao, Kai Huang

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Although c-Jun/c-Fos (activator protein 1, AP1) contributes importantly to Ang II-induced cardiac fibrosis through induction of extracellular matrix protein over-expression in cardiac fibroblasts, the mechanism by which Ang II promotes c-Jun/c-Fos transactivation remains unclear. In this study, we demonstrated that c-Fos and c-Jun were poly(ADP-ribosyl)ated in cultured cardiac fibroblasts. Southwestern blot and EMSA assays showed that incubation of nuclear extracts with NAD+ and active DNA increased the basal DNA binding activities of c-Jun (31.0 ± 1.0%, P < 0.01) and AP1 (14.2 ± 3.1%, P < 0.01); incubation of recombinant c-Fos or/and c-Jun with PARP-1, NAD+ and active DNA increased the basal DNA binding activities of c-Jun (48.3 ± 4.2%, P < 0.01) and AP1 (21.2 ± 1.5%, P < 0.01). Treatment with Ang II promoted PARP-1 activation and enhanced poly(ADP-ribosyl)ation of c-Fos (14.1 + 1.1%, P < 0.01) and c-Jun (15.5 ± 5.6%, P < 0.01). Ang II also increased the basal DNA binding activities of c-Jun (13.5 ± 2.4%, P < 0.01) and AP1 (18.7 ± 3.5%, P < 0.01) in cultured cells. Inhibition of PARP-1 by PJ34 or siRNA effectively prevented Ang II-induced increases in the DNA binding of c-Jun and AP1, and decreased AP1-driven transcription (including collagen Iα1 and IIIα1, MMP-9 and TIMP-1). This study illustrated that c-Jun and c-Fos were poly(ADP-ribosyl)ated by PARP-1, and poly(ADP-ribosyl)ation enhanced the DNA binding of AP1. Ang II promoted poly(ADP-ribosyl)ation of c-Jun and c-Fos through activation of PARP-1 and, subsequently, enhanced AP1-driven transcription in cardiac fibroblasts.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Keywords

  • Activator protein 1
  • Angiotensin II
  • c-Fos
  • c-Jun
  • Cardiac fibroblast
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Angiotensin II promotes poly(ADP-ribosyl)ation of c-Jun/c-Fos in cardiac fibroblasts'. Together they form a unique fingerprint.

  • Cite this