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Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with the β1 and β3 but not β2 adrenergic receptors, and induces apoptosis

  • Ion channels, receptors and transporters
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Abstract

Hydrogen sulfide (H2S) as a novel gasotransmitter regulates variety of processes, including calcium transport systems. Sodium calcium exchanger (NCX) is one of the key players in a regulation calcium homeostasis. Thus, the aims of our work were to determine effect of sulfide signaling on the NCX type 1 (NCX1) expression and function in HeLa cells, to investigate the relationship of β-adrenergic receptors with the NCX1 in the 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) phosphinodithioate—GYY4137. 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 upregulation of β-adrenergic receptors. Indeed, GYY4137 increased expression of β1 and β3 (but not β2) 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 regulation of the NCX1, β1 and β3 adrenergic receptors, their co-localization, and stimulation of apoptosis, which might be of a potential importance in cancer treatment.

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Acknowledgments

This work was supported by grants APVV 51-0045-11, VEGA 2/0095/13 and Center of Excellence for Studying Metabolic Aspects of Development, Diagnostics and Treatment of the Oncologic Diseases (CEMAN). Project implementation, DNA-DG: ITMS 26240220058, was supported by the Research & Development Operational Programme funded by the ERDF.

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  1. Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences (SAS), Vlarska 5, 833 34, Bratislava, Slovak Republic

    Jana Markova, Sona Hudecova, Andrea Soltysova, Marta Sirova, Lubomira Lencesova, Karol Ondrias & Olga Krizanova

  2. Institute of Virology, SAS, Bratislava, Slovakia

    Lucia Csaderova

  3. Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia

    Andrea Soltysova

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  1. Jana Markova
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Correspondence to Olga Krizanova.

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Markova, J., Hudecova, S., Soltysova, A. et al. Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with the β1 and β3 but not β2 adrenergic receptors, and induces apoptosis. Pflugers Arch - Eur J Physiol 466, 1329–1342 (2014). https://doi.org/10.1007/s00424-013-1366-1

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