Sodium/calcium exchanger is involved in apoptosis induced by H2S in tumor cells through decreased levels of intracellular pH

Authors

SZADVÁRI Ivan HUDECOVÁ Soňa CHOVANCOVÁ Barbora MATÚŠKOVÁ Miroslava CHOLUJOVÁ Dana LENČEŠOVA Ľubomíra VALERIÁN David ONDRIAS Karol BABULA Petr KRIŽANOVÁ Oľga

Year of publication 2019
Type Article in Periodical
Magazine / Source NITRIC OXIDE-BIOLOGY AND CHEMISTRY
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.sciencedirect.com/science/article/pii/S1089860318303343?via%3Dihub
Doi http://dx.doi.org/10.1016/j.niox.2019.02.011
Keywords Apoptosis; Hydrogen sulfide; Intracellular acidification; Sodium/calcium exchanger; Sodium/hydrogen exchanger
Description We explored possibility that sodium/calcium exchanger 1 (NCX1) is involved in pH modulation and apoptosis induction in GYY4137 treated cells. We have shown that although 10 days treatment with GYY4137 did not significantly decreased volume of tumors induced by colorectal cancer DLD1 cells in nude mice, it already induced apoptosis in these tumors. Treatment of DLD1 and ovarian cancer A2780 cells with GYY4137 resulted in intracellular acidification in a concentration-dependent manner. We observed increased mRNA and protein expression of both, NCX1 and sodium/hydrogen exchanger 1 (NHE1) in DLD1-induced tumors from GYY4137-treated mice. NCX1 was coupled with NHE1 in A2780 and DLD1 cells and this complex partially disintegrated after GYY4137 treatment. We proposed that intracellular acidification is due to uncoupling of NCX1/NHE1 complex rather than blocking of the reverse mode of NCX1, probably due to internalization of NHE1. Results might contribute to understanding molecular mechanism of H2S induced apoptosis in tumor cells.
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