title: Hypoxic conditions increases H₂S-induced ER stress in A2870 cells.
abstract: 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.
authors: Biomedical Research Center, Institute for Clinical and Translational Research, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovak Republic.
authors: Lubomira
authors: L
authors: Lencesova
authors: Biomedical Research Center, Institute for Clinical and Translational Research, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovak Republic.
authors: Miroslav
authors: M
authors: Vlcek
authors: Biomedical Research Center, Institute for Clinical and Translational Research, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovak Republic.
authors: Olga
authors: O
authors: Krizanova
authors: Biomedical Research Center, Institute for Clinical and Translational Research, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovak Republic. sona.hudecova@savba.sk.
authors: Sona
authors: S
authors: Hudecova
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology
chemical_list: D000600:Amino Acids, Dicarboxylic; C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; C040947:oxalylglycine; D006862:Hydrogen Sulfide
keywords: Apoptosis; Cancer; H2S; Hypoxia; IP3 receptors; Intracellular calcium