Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 211-215 |
| Number of pages | 5 |
| Journal | European Journal of Pharmaceutical Sciences |
| Volume | 48 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jan 23 2013 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
Cite this
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.
In: European Journal of Pharmaceutical Sciences, Vol. 48, No. 1-2, 23.01.2013, p. 211-215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells
AU - Kida, Michiya
AU - Sugiyama, Toru
AU - Yoshimoto, Takanobu
AU - Ogawa, Yoshihiro
PY - 2013/1/23
Y1 - 2013/1/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejps.2012.11.001
DO - 10.1016/j.ejps.2012.11.001
M3 - Article
VL - 48
SP - 211
EP - 215
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
IS - 1-2
ER -