Redox factor-1 contributes to the regulation of progression from G0/G1 to S by PDGF in vascular smooth muscle cells

Tongrong He, Neal L. Weintraub, Prabhat C. Goswami, Papri Chatterjee, Dawn M. Flaherty, Frederick E. Domann, Larry W. Oberley

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Redox factor-1 (Ref-1/APE), a multifunctional DNA base excision repair and redox regulation enzyme, plays an important role in oxidative signaling, transcription factor regulation, and cell cycle control. We hypothesized that Ref-1 plays a regulatory role in smooth muscle cell (SMC) proliferation induced by PDGF. Ref-1 antisense oligodeoxynucleotides (AODN), which diminished the level of Ref-1 protein in SMCs by ∼50%, inhibited PDGF-BB (composed of the homodimer of B-polypeptide chain)-induced [3H]thymidine incorporation compared with control oligodeoxynucleotides. Ref-1 AODN inhibited PDGF-BB-induced S phase entry by ∼63%, which was overcome by overexpression of Ref-1 by adenoviral-mediated gene transfer. Overexpression of Ref-1 alone without PDGF enhanced SMC entry into the S phase. Furthermore, decreasing Ref-1 protein by treatment of SMCs with Ref-1 AODN, or by immunodepletion of Ref-1 from nuclear extracts, inhibited PDGF-BB-induced activator protein-1 (AP-1) DNA binding activity. Chemical reduction restored the AP-1 DNA binding in Ref-1-depleted nuclear extracts. These results suggest that Ref-1 contributes to the regulation of PDGF-BB-stimulated cell cycle progression from G0/G1 to S in SMCs, with one of the possible steps being redox-regulation of AP-1 by Ref-1 protein.

Original languageEnglish (US)
Pages (from-to)H804-H812
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number2 54-2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Activator protein-1
  • Antisense
  • Cell cycle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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