Hypoxia - a state of lower
oxygen demand-is responsible for a higher aggressiveness of
tumors and therefore a worse prognosis. During
hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and
calcium transport.
Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular
calcium transport systems in
hypoxia and in cells grown in standard culture conditions. For all experiments, we used
ovarian cancer cell line (A2780). H2S is a novel
gasotransmitter, known to be involved in a modulation of several
calcium transport systems, thus resulting in altered calcium signaling. Two models of
hypoxia were used in our study-chemical (induced by
dimethyloxallyl glycine) and 2 % O2
hypoxia, both combined with a treatment using a slow H2S donor
GYY4137. In
hypoxia, we observed rapid changes in cytosolic and reticular
calcium levels compared to cells grown in standard culture conditions, and these changes were even more exagerrated when combined with the
GYY4137. Changes in a
calcium homeostasis result from IP3 receptor´s up-regulation and down-regulation of the SERCA 2, which leads to a development of the endoplasmic reticulum stress. Based on our results, we propose a higher vulnerability of
calcium transport systems to H2S regulation under
hypoxia.