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- Title
Hypoxic conditions increases HS-induced ER stress in A2870 cells.
- Authors
Lencesova, Lubomira; Vlcek, Miroslav; Krizanova, Olga; Hudecova, Sona
- 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 HS 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). HS 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 % O hypoxia, both combined with a treatment using a slow HS 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 IP 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 HS regulation under hypoxia.
- Subjects
PATHOPHYSIOLOGY of anoxemia; HYPOXIA-inducible factor 1; ENDOPLASMIC reticulum; HYPOXEMIA; INTRACELLULAR calcium; CANCER cell culture; PHYSIOLOGY; THERAPEUTICS
- Publication
Molecular & Cellular Biochemistry, 2016, Vol 414, Issue 1/2, p67
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-016-2659-4