Extended hypoxia-mediated H2S production provides for long-term oxygen sensing

Kenneth R. Olson, Yan Gao, Eric R. DeLeon, Troy A. Markel, Natalie Drucker, David Boone, Matt Whiteman, Andrea K. Steiger, Michael D. Pluth, Charles R. Tessier, Robert V. Stahelin

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Abstract

Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24-48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical-derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur-specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21% O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21% to 10%, 5% and 1% O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21% to 5% except for HTC116 cells where 1% O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2-7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2-sensing mechanism in a variety of cells.

Original languageEnglish (US)
Article numbere13368
JournalActa Physiologica
Volume228
Issue number3
DOIs
StatePublished - Mar 1 2020

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Keywords

  • hypoxia
  • mitochondria
  • oxygen tension
  • sulphur metabolism

ASJC Scopus subject areas

  • Physiology

Cite this

Olson, K. R., Gao, Y., DeLeon, E. R., Markel, T. A., Drucker, N., Boone, D., Whiteman, M., Steiger, A. K., Pluth, M. D., Tessier, C. R., & Stahelin, R. V. (2020). Extended hypoxia-mediated H2S production provides for long-term oxygen sensing. Acta Physiologica, 228(3), [e13368]. https://doi.org/10.1111/apha.13368