Redox factor-1 contributes to the regulation of progression from G0/G1 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: United States 01.08.2003
• Subjects: Angiogenesis Inducing Agents - pharmacology; Animals; Aorta, Thoracic - cytology; Carbon-Oxygen Lyases - genetics; Carbon-Oxygen Lyases - metabolism; Cells, Cultured; DNA-(Apurinic or Apyrimidinic Site) Lyase; G1 Phase - drug effects; G1 Phase - physiology; Gene Expression; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Oligoribonucleotides, Antisense - pharmacology; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; Resting Phase, Cell Cycle - drug effects; Resting Phase, Cell Cycle - physiology; S Phase - drug effects; S Phase - physiology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01080.2002

1 Free Radical and Radiation Biology Program, Department of Radiation Oncology, 2 Department 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 [ 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. 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 ).