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The mechanisms underlying the sensing of hypoxia and subsequent coupling to sodium-transporting molecules remain unclear. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) has recently been recognized as a cellular signaling molecule whose intracellular concentrations critically depend on oxygen levels. Therefore, it was questioned whether endogenously produced H<jats:sub>2<\/jats:sub>S contributes to hypoxic inhibition of sodium transport. In electrophysiological Ussing chamber experiments, hypoxia was established by decreasing oxygen concentrations in the chambers. Hypoxia concentration dependently and reversibly decreased amiloride-sensitive sodium absorption by cultured H441 monolayers and freshly dissected porcine tracheal epithelia due to inhibition of basolateral Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase. Exogenous application of H<jats:sub>2<\/jats:sub>S by the sulfur salt Na<jats:sub>2<\/jats:sub>S mimicked the effect of hypoxia and inhibited amiloride-sensitive sodium absorption by both tissues in an oxygen-dependent manner. Hypoxia increased intracellular concentrations of H<jats:sub>2<\/jats:sub>S and decreased the concentration of polysulfides. Pretreatment with the cystathionine-\u03b3-lyase inhibitor d\/l-propargylglycine (PAG) decreased hypoxic inhibition of sodium transport by H441 monolayers, whereas inhibition of cystathionine-\u03b2-synthase (with aminooxy-acetic acid; AOAA) or 3-mercaptopyruvate sulfurtransferase (with aspartate) had no effect. Inhibition of all of these H<jats:sub>2<\/jats:sub>S-generating enzymes with a combination of AOAA, PAG, and aspartate decreased the hypoxic inhibition of sodium transport by H441 cells and pig tracheae and decreased H<jats:sub>2<\/jats:sub>S production by tracheae. These data suggest that airway epithelial cells endogenously produce H<jats:sub>2<\/jats:sub>S during hypoxia, and this contributes to hypoxic inhibition of transepithelial sodium absorption. <\/jats:p>","DOI":"10.1152\/ajpregu.00177.2016","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T03:28:48Z","timestamp":1469071728000},"page":"R607-R617","source":"Crossref","is-referenced-by-count":14,"title":["Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption"],"prefix":"10.1152","volume":"311","author":[{"given":"Nicole C.","family":"Krause","sequence":"first","affiliation":[{"name":"Institute for Animal Physiology, Justus-Liebig-University, Giessen, Germany; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna S.","family":"Kutsche","sequence":"additional","affiliation":[{"name":"Institute for Animal Physiology, Justus-Liebig-University, Giessen, Germany; 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