Carotid Body O2 Sensing requires H2S-dependent Persulfidation of Olfactory Receptor 78
| Autor: | Ying-Jie Peng, Jayasri Nanduri, Ning Wang, Vytautas Bindokas, Aaron Fox, Thibaut Vignane, Milos Filipovic, Nanduri Prabhakar |
|---|---|
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiology. 38 |
| ISSN: | 1548-9221 1548-9213 |
| Popis: | Hydrogen sulfide (H2S) is implicated in O2 sensing by the carotid body(CB) to stimulate breathing response to hypoxia. Present study shows hydrogen sulfide-dependent persulfidation (S-sulfhydration) of olfactory receptor 78 (Olfr78) as an integral component of carotid body O2 sensing. H2S increased cAMP production (index of Olfr78 activation) in HEK-293 cells expressing Olfr78 as measured by cAMP fluorescent biosensor, in a dose-dependent manner with an ED50 of 25μM. H2S as well as hypoxia increased persulfidation in the carotid body glomus cells and these responses were absent in cells Olfr78 as well as CTH (CSE) null mice. MS/MS analysis showed that persulfidation of Cys240 increased in a time-dependent manner with H2S. Alpha fold modelling of Olfr78 showed Cys240 in the interface of the cytosol and the membrane facilitating water accessibility of sulfur atom in cysteine. Substituting Cys240 with alanine blocked Olfr78 activation by H2S as indicated by absence of increased cAMP fluorescence in HEK-293 cells and impaired trafficking of Olfr78 protein to the cell membrane, consistent with the Alpha fold model prediction of Cys240 location near the surface of the Olfr78. Hypoxia and H2S stimulated ex vivo CB sensory activity and elevated intracellular calcium of glomus cells in wild type but not Olfr78 mutants. Intravenous administration of H2S increased efferent phrenic nerve activity in a dose-dependent manner, and the responses were absent in Olfr78 mutants. These results suggest that H2S through redox modification of Cys240 of Olfr78 participates in O2 sensing by the CB to regulate breathing. Supported by NIH-HLBI P01-HL-44454 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|