Molecular and Cellular Biochemistry

, Volume 414, Issue 1–2, pp 67–76 | Cite as

Hypoxic conditions increases H2S-induced ER stress in A2870 cells

  • Lubomira Lencesova
  • Miroslav Vlcek
  • Olga Krizanova
  • Sona Hudecova


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.


H2Hypoxia Intracellular calcium IP3 receptors Cancer Apoptosis 



This work was supported by grants APVV-14-0351, APVV-0045-11, and VEGA 2/0082/16.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lubomira Lencesova
    • 1
  • Miroslav Vlcek
    • 1
  • Olga Krizanova
    • 1
  • Sona Hudecova
    • 1
  1. 1.Biomedical Research Center, Institute for Clinical and Translational ResearchSlovak Academy of SciencesBratislavaSlovak Republic

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