Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation
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- 作者：Sang Woong Park (1)
Hyun Ju Noh (1)
Dong Jun Sung (2)
Jae Gon Kim (3)
Jeong Min Kim (1)
Shin-Young Ryu (4)
KyeongJin Kang (5)
Bokyung Kim (1)
Young Min Bae (1)
Hana Cho (3) - 关键词：H2O2 ; Kv channel ; Mesenteric artery ; S ; glutathionylation ; Oxidative stress
- 刊名：Pflügers Archiv - European Journal of Physiology
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：467
- 期：2
- 页码：285-297
- 全文大小：1,622 KB
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Hyun Ju Noh (1)
Dong Jun Sung (2)
Jae Gon Kim (3)
Jeong Min Kim (1)
Shin-Young Ryu (4)
KyeongJin Kang (5)
Bokyung Kim (1)
Young Min Bae (1)
Hana Cho (3)
1. Department of Physiology, Institute of Functional Genomics, Research Institute of Medical Science, School of Medicine, Konkuk University, Choongju, 380-701, Korea
2. Division of Sport Science, College of Science and Technology, Konkuk University, Choongju, Korea
3. Department of Physiology and Samsung Biomedical Research Institute, School of Medicine, Sungkyunkwan University, Suwon, Korea
4. Department of Physiology and Biomembrane Plasticity Research Center, College of Medicine, Seoul National University, Seoul, Korea
5. Department of Anatomy and Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, Korea - 刊物主题：Human Physiology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1432-2013
文摘
Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H2O2 depending 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-glutathionylation, 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.