Redox factor-1 contributes to the regulation of progression from G0/G1 to S by PDGF in vascular smooth muscle cells.
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 approximately 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 approximately 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.
Free Radical and Radiation Biology Program, Dept. of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USA.
Tongrong
T
He
Neal L
NL
Weintraub
Prabhat C
PC
Goswami
Papri
P
Chatterjee
Dawn M
DM
Flaherty
Frederick E
FE
Domann
Larry W
LW
Oberley
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D000077214:Becaplermin; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D020320:Oligoribonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018808:Transcription Factor AP-1; D000077214:Becaplermin; D019757:Carbon-Oxygen Lyases; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase