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 language | English (US) |
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Pages (from-to) | 902-910 |
Number of pages | 9 |
Journal | Circulation research |
Volume | 95 |
Issue number | 9 |
DOIs | |
State | Published - Oct 29 2004 |
Externally published | Yes |
Keywords
- H-ras
- Hypertension
- Redox
- eNOS
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine