Extended hypoxia-mediated H 2 S production provides for long-term oxygen sensing.

Autor: Olson KR; Indiana University School of Medicine-South Bend, South Bend, Indiana., Gao Y; Indiana University School of Medicine-South Bend, South Bend, Indiana., DeLeon ER; Indiana University School of Medicine-South Bend, South Bend, Indiana.; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana., Markel TA; Indiana University School of Medicine, Riley Hospital for Children at IU Health, Indianapolis, Indiana., Drucker N; Indiana University School of Medicine, Riley Hospital for Children at IU Health, Indianapolis, Indiana., Boone D; Indiana University School of Medicine-South Bend, South Bend, Indiana., Whiteman M; University of Exeter, Exeter, UK., Steiger AK; Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon., Pluth MD; Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon., Tessier CR; Indiana University School of Medicine-South Bend, South Bend, Indiana., Stahelin RV; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2020 Mar; Vol. 228 (3), pp. e13368. Date of Electronic Publication: 2019 Sep 18.
DOI: 10.1111/apha.13368
Abstrakt: 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.
(© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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