Hydrogen sulfide‐induced apoptosis of human aorta smooth muscle cells via the activation of mitogen‐activated protein kinases and caspase‐3

Abstract

The endogenous production of hydrogen sulfide (H2S) and its physiological functions, including membrane hyperpolarization and smooth muscle cell relaxation, position this gas well in the family of gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). In this study, we demonstrate that H2S at physiologically relevant concentrations induced apoptosis of human aorta smooth muscle cells (HASMCs). Exposure of HASMCs to H2S did not induce necrosis as verified with Trypan blue exclusion and LDH release analysis. After inhibiting endogenous H2S production, exogenous H2S induced much more significant apoptosis, which was not altered by the presence of albumin or glutathione. H2S treatment increased the activities of ERK and p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase activity. Suppression of extracellular signal-regulated kinase (ERK) activity, but not of p38 activity, inhibited the H2S-induced apoptosis of HASMCs. The activation of ERK by H2S in HASMCs was accompanied by increased caspase-3 activity. Inhibition of caspase-3 by AC-DEVD-CHO attenuated the H2S-induced cell apoptosis. Inhibition of ERK by U0126 decreased caspase-3 activity, whereas AC-DEVD-CHO did not alter ERK activity. In conclusion, exogenous H2S induces apoptosis of HASMCs, which is significantly affected by the endogenous H2S level. Of the three investigated MAPKs, only ERK played an active role in mediating H2S-induced apoptosis of HASMCs by activating caspase-3. These findings may help reveal novel mechanisms for many diseases linked to H2S-related abnormal cellular proliferation and apoptosis.

Apoptosis, metallothionein, and bioavailable metals in domestic mice (Mus musculus L.) from a human-inhabited volcanic area

“…The other three metals are also known to cause apoptosis in several organs (Sensi et al 1999;Singh et al 1999;Jiang et al 2001;Lin et al 2003;Toimela and Tähti 2004;Banasik et al 2005;Xu et al 2006). Besides metals, gases like hydrogen sulfide (H 2 S) and sulfur dioxide (SO 2 ), as well as sulfuric acid aerosols, present in the air of Furnas should be pondered since an association between H 2 S and SO 2 and apoptosis in lung and aorta cells has been found elsewhere (Yang et al 2004;Bai and Meng 2005). The levels of MT (IDI MT ) were higher in mice from Furnas than in those from Rabo de Peixe.…”

Highly sensitive sulphide mapping in live cells by kinetic spectral analysis of single Au-Ag core-shell nanoparticles

“…H 2 S equilibrates with aqueous sulphides (HS À and S 2 À ) in biological environments and has vital roles in various physiological and pathological processes, including vasorelaxation 5 , angiogenesis 6 , cerebral microcirculation 7 , neurotransmission 8,9 , inflammation 10 , apoptosis 11 , insulin signalling inhibition 12 , oxygen sensing 13 and energy production in mitochondria 14 . Meanwhile, the H 2 S levels are related to a number of diseases, such as Down syndrome 15 , Alzheimer disease 16 , hyperglycaemia 17 , ischaemia 18 and so on.…”

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

“…[3][4][5] Altered cell proliferation or apoptosis induced by H 2 S has also been widely reported. [6][7][8][9][10] Endogenous production and physiological function of H 2 S in pancreas have been studied with identification of both CBS and CSE in rat pancreatic tissues or cloned rat pancreatic b-cell line. 11,12 In recent years, pathophysiological implications of the CSE/H 2 S system in diabetes have been reported.…”