Role of reactive oxygen species and sulfide-quinone oxoreductase in hydrogen sulfide-induced contraction of rat pulmonary arteries
| Autor: | Prieto-Lloret, Jesús, Snetkov, Vladimir A., Shaifta, Yasin, Docio, Inmaculada, Connolly, Michelle J., MacKay, Charles E., Knock, Greg A., Ward, Jeremy P. T., Aaronson, Philip I. |
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| Přispěvatelé: | Wellcome Trust, British Heart Foundation, European Commission, Knock, Greg A. [0000-0001-7037-4268], Knock, Greg A. |
| Rok vydání: | 2018 |
| Předmět: |
reactive oxygen species
Male Electron Transport Complex I Hydrogen sulfide hydrogen sulfide sulfide-quinone oxoreductase Pulmonary Artery Sulfides Muscle Smooth Vascular Rats Mitochondria Pulmonary artery Protein kinase C Benzoquinones Animals Rat rat Calcium Rats Wistar Oxidoreductases Reactive oxygen species Research Article protein kinase C |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname American Journal of Physiology-Lung Cellular and Molecular Physiology |
| Popis: | Application of H2S (“sulfide”) elicits a complex contraction in rat pulmonary arteries (PAs) comprising a small transient contraction (phase 1; Ph1) followed by relaxation and then a second, larger, and more sustained contraction (phase 2; Ph2). We investigated the mechanisms causing this response using isometric myography in rat second-order PAs, with Na2S as a sulfide donor. Both phases of contraction to 1,000 μM Na2S were attenuated by the pan-PKC inhibitor Gö6983 (3 μM) and by 50 μM ryanodine; the Ca2+ channel blocker nifedipine (1 μM) was without effect. Ph2 was attenuated by the mitochondrial complex III blocker myxothiazol (1 μM), the NADPH oxidase (NOX) blocker VAS2870 (10 μM), and the antioxidant TEMPOL (3 mM) but was unaffected by the complex I blocker rotenone (1 μM). The bath sulfide concentration, measured using an amperometric sensor, decreased rapidly following Na2S application, and the peak of Ph2 occurred when this had fallen to ~50 μM. Sulfide caused a transient increase in NAD(P)H autofluorescence, the offset of which coincided with development of the Ph2 contraction. Sulfide also caused a brief mitochondrial hyperpolarization (assessed using tetramethylrhodamine ethyl ester), followed immediately by depolarization and then a second more prolonged hyperpolarization, the onset of which was temporally correlated with the Ph2 contraction. Sulfide application to cultured PA smooth muscle cells increased reactive oxygen species (ROS) production (recorded using L012); this was absent when the mitochondrial flavoprotein sulfide-quinone oxoreductase (SQR) was knocked down using small interfering RNA. We propose that the Ph2 contraction is largely caused by SQR-mediated sulfide metabolism, which, by donating electrons to ubiquinone, increases electron production by complex III and thereby ROS production. J. Prieto-Lloret, V. Snetkov, and Y. Shaifta were supported by Wellcome Trust Programme Grant 087776 (to J. P. Ward and P. I. Aaronson). M. J. Connolly and C. E. MacKay were supported by PhD Studentships from British Heart Foundation Grants FS/05/117/19967 (to P. I. Aaronson) and FS/12/43/29608 (to G. A. Knock). I. Docio was supported by an Erasmus Traineeship. |
| Databáze: | OpenAIRE |
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