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Extended hypoxia‐mediated H 2 S production provides for long‐term oxygen sensing
Author(s) -
Olson Kenneth R.,
Gao Yan,
DeLeon Eric R.,
Markel Troy A.,
Drucker Natalie,
Boone David,
Whiteman Matt,
Steiger Andrea K.,
Pluth Michael D.,
Tessier Charles R.,
Stahelin Robert V.
Publication year - 2020
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13368
Subject(s) - hek 293 cells , chemistry , oxygen , endogeny , mesenchymal stem cell , hypoxia (environmental) , biochemistry , microbiology and biotechnology , biology , receptor , organic chemistry
Aim Numerous studies have shown that H 2 S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H 2 S also serves in extended oxygen sensing. Methods Here, we compare the effects of extended exposure (24‐48 hours) to varying O 2 tensions on H 2 S 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 H 2 S in 21% O 2 and H 2 S production was increased at lower O 2 tensions. Decreasing O 2 from 21% to 10%, 5% and 1% O 2 progressively increased H 2 S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H 2 S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H 2 S production in all other cells and PTE increased when O 2 was lowered from 21% to 5% except for HTC116 cells where 1% O 2 was necessary to increase H 2 S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H 2 S n , where n = 2‐7), the key signalling metabolite of H 2 S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion These results show that cellular H 2 S is increased during extended hypoxia and they suggest this is a continuously active O 2 ‐sensing mechanism in a variety of cells.