Redox factor-1 contributes to the regulation of progression from G 0 /G 1 to S by PDGF in vascular smooth muscle cells

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 285; no. 2; pp. H804 - H812
• Main Authors: He, Tongrong, Weintraub, Neal L., Goswami, Prabhat C., Chatterjee, Papri, Flaherty, Dawn M., Domann, Frederick E., Oberley, Larry W.
• Format: Journal Article
• Language: English
• Published: 01.08.2003
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01080.2002

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 [ 3 H]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 G 0 /G 1 to S in SMCs, with one of the possible steps being redox-regulation of AP-1 by Ref-1 protein.