Apurinic/apyrmidinic endonuclease 1 regulates endothelial NO production and vascular tone

Academic Article

Abstract

  • The dual-function protein apurinic/apyrmidinic 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.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Jeon BH; Gupta G; Park YC; Qi B; Haile A; Khanday FA; Liu YX; Kim JM; Ozaki M; White AR
  • Start Page

  • 902
  • End Page

  • 910
  • Volume

  • 95
  • Issue

  • 9