P68 H2S induces apoptosis through calcium and catecholamine modulation in HeLa cells

Abstract

Hydrogen sulfide (H2S) as a novel gasotransmitter regulates variety of processes, among them calcium transport systems. Sodium calcium exchanger (NCX) is one of key players in a regulation of calcium homeostasis. Thus, the aim of our work was to determine effect of sulfide signaling on the NCX type 1 (NCX1) expression and function in HeLa cells, to investigate relationship of beta-adrenergic receptors with the NCX1 in a presence and/or absence of H2S and to determine physiological importance of this potential communication. As a H2S donor we used morpholin-4-ium-4-methoxyphenyl (morpholino) phosphino-dithioate (GYY4137; 10 μ M). We observed increased levels of the NCX1 mRNA, protein and activity after 24 h of GYY4137 treatment. This increase was accompanied by elevated cAMP due to the GYY4137 treatment, which was completely abolished, when NCX1 was silenced. Increased cAMP levels would point to up-regulation of beta-adrenergic receptors. Indeed, GYY4137 increased expression of beta1 and beta3 (but not beta2) adrenergic receptors. These receptors co-precipitated, co-localized with the NCX1 and induced apoptosis in the presence of H2S. Our results suggest that sulfide signaling plays a role in the apoptosis induction through the up-regulation and mutual interaction of the NCX1, beta1 and beta3 adrenergic receptors, which might be of a potential importance in a cancer treatment. This work was supported by grants CEMAN and APVV51-0045-11.