486회

TITLE: Hydrogen peroxide as a modulator of arterial function

SPEAKER : Young Min Bae (Department of Physiology ,Konkuk University School of Medicine)

Education  

  1998. 03-2001. 02: 박사, 서울의대 생리학교실

  1996. 02-1998. 02: 석사, 서울의대 생리학교실

  1991. 03-1996. 02: 학사(수의사), 서울수의대

Research Experiences

  2014.03  -  현재:  실험동물센터장, 건국대학교 산학협력단

  2001.09  -  현재:  교수, 건국대학교 의학전문대학원 생리학교실

  2001.03-2001.08:  박사 후 연구원, 서울의대 생리학교실

Papers

Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation. Pflügers Arch - Eur J Physiol. 2014 Apr 23.외 40여편

ABSTRACT

Hydrogen peroxide (H₂O₂) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H₂O₂depending on the vascular bed and experimental conditions, this study was performed to assess whether H₂O₂ acts as a vasodilator in the rat mesenteric artery and if so, to determine the underlying mechanisms. H₂O₂ elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of H₂O₂ was reversed by treatment with dithiothreitol. H₂O₂-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca²⁺-activated K⁺channels and inward-rectifier K⁺ channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that H₂O₂ increased Kv currents in a concentration-dependent manner. H₂O₂ speeded up Kv channel activation and shifted steady-state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The H₂O₂-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionlyation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of H₂O₂. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of H₂O₂ to stimulate Kv channels. Not only was the H₂O₂ stimulatory effect much weaker, but the inhibitory effect of H₂O₂ was unmasked. These data suggest that H₂O₂ activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to H₂O₂. Supplementary mechanics data from hypertensive rat that are supporting this basal redox status hypothesis would be discussed.

Keywords: H₂O₂, Kv channel, mesenteric artery, S-glutathionylation, oxidative stress, hypertension.