First Author | Jeon BH | Year | 2004 |
Journal | Circ Res | Volume | 95 |
Issue | 9 | Pages | 902-10 |
PubMed ID | 15472121 | Mgi Jnum | J:102294 |
Mgi Id | MGI:3607239 | Doi | 10.1161/01.RES.0000146947.84294.4c |
Citation | Jeon BH, et al. (2004) Apurinic/apyrimidinic endonuclease 1 regulates endothelial NO production and vascular tone. Circ Res 95(9):902-10 |
abstractText | The dual-function protein apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/ref-1) is essential for DNA repair and also governs the reductive activation of many redox-sensitive transcription factors. We examined the role of APE1/ref-1 in regulation of endothelium-dependent tone and systemic blood pressure. APE1/ref-1+/- mice have impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/ref-1 upregulates H-ras expression and leads to H-ras-mediated, phosphoinositide-3 kinase/Akt kinase-dependent calcium sensitization of endothelial NO synthase (eNOS), stimulating NO production. The reducing property of APE1/ref-1 is essential for upregulation of H-ras and for the calcium sensitization of eNOS. These findings uncover a novel physiological role for APE1/ref-1 in regulating vascular tone by governance of eNOS activity and bioavailable NO. |