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Am J Physiol Heart Circ Physiol 285: H804-H812, 2003. First published May 1, 2003; doi:10.1152/ajpheart.01080.2002
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Redox factor-1 contributes to the regulation of progression from G0/G1 to S by PDGF in vascular smooth muscle cells

Tongrong He,1 Neal L. Weintraub,2 Prabhat C. Goswami,1 Papri Chatterjee,2 Dawn M. Flaherty,2 Frederick E. Domann,1 and Larry W. Oberley1

1Free Radical and Radiation Biology Program, Department of Radiation Oncology, 2Department of Internal Medicine, The University of Iowa, Iowa City, Iowa 52242

Submitted 12 December 2002 ; accepted in final form 28 April 2003

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.

activator protein-1; cell cycle; antisense


Address for reprint requests and other correspondence: L. W. Oberley at Free Radical and Radiation Biology Program, Dept. of Radiation Oncology, The Univ. of Iowa, Iowa City, IA 52242-1181 (E-mail: larry-oberley{at}uiowa.edu).




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