Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells

Michiya Kida, Toru Sugiyama, Takanobu Yoshimoto, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿記事

43 引用 (Scopus)

抄録

Hydrogen sulfide (H 2 S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H 2 S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H 2 S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H 2 S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H 2 S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H 2 S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.

元の言語英語
ページ(範囲)211-215
ページ数5
ジャーナルEuropean Journal of Pharmaceutical Sciences
48
発行部数1-2
DOI
出版物ステータス出版済み - 1 23 2013
外部発表Yes

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Hydrogen Sulfide
Nitric Oxide Synthase Type III
Nitric Oxide
Endothelial Cells
Calcium
Nitric Oxide Synthase
Dantrolene
Vasodilator Agents
Phosphorylation
Phosphoserine
Inositol 1,4,5-Trisphosphate Receptors
Endothelium-Dependent Relaxing Factors
Ryanodine Receptor Calcium Release Channel
Cardiovascular System
Phosphatidylinositol 3-Kinases
Vasodilation
Endoplasmic Reticulum
Antihypertensive Agents
Cultured Cells
sodium bisulfide

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

これを引用

Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells. / Kida, Michiya; Sugiyama, Toru; Yoshimoto, Takanobu; Ogawa, Yoshihiro.

:: European Journal of Pharmaceutical Sciences, 巻 48, 番号 1-2, 23.01.2013, p. 211-215.

研究成果: ジャーナルへの寄稿記事

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