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

Byeong Hwa Jeon, Gaurav Gupta, Young Chul Park, Bing Qi, Azeb Haile, Firdous A. Khanday, Yan Xia Liu, Jin Man Kim, Michitaka Ozaki, Anthony R. White, Dan E. Berkowitz, Kaikobad Irani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)902-910
Number of pages9
JournalCirculation research
Volume95
Issue number9
DOIs
StatePublished - Oct 29 2004

Keywords

  • H-ras
  • Hypertension
  • Redox
  • eNOS

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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