Protein kinase G-regulated production of H2S governs oxygen sensing

Guoxiang Yuan, Chirag Vasavda, Ying Jie Peng, Vladislav V. Makarenko, Gayatri Raghuraman, Jayasri Nanduri, Moataz M. Gadalla, Gregg L Semenza, Ganesh K. Kumar, Solomon H Snyder, Nanduri R. Prabhakar

Research output: Contribution to journalArticle

Abstract

Reflexes initiated by the carotid body, the principal O2-sensing organ, are critical for maintaining cardiorespiratory homeostasis during hypoxia. O2 sensing by the carotid body requires carbon monoxide (CO) generation by heme oxygenase-2 (HO-2) and hydrogen sulfide (H2S) synthesis by cystathionine-γ-lyase (CSE). We report that O2 stimulated the generation of CO, but not that of H2S, and required two cysteine residues in the heme regulatory motif (Cys265 and Cys282) of HO-2. CO stimulated protein kinase G (PKG)-dependent phosphorylation of Ser377 of CSE, inhibiting the production of H2S. Hypoxia decreased the inhibition of CSE by reducing CO generation resulting in increased H2S, which stimulated carotid body neural activity. In carotid bodies from mice lacking HO-2, compensatory increased abundance of nNOS (neuronal nitric oxide synthase) mediated O2 sensing through PKG-dependent regulation of H2S by nitric oxide. These results provide a mechanism for how three gases work in concert in the carotid body to regulate breathing.

Original languageEnglish (US)
Article numberra37
JournalScience Signaling
Volume8
Issue number373
DOIs
StatePublished - Apr 21 2015

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Cyclic GMP-Dependent Protein Kinases
Carotid Body
Hydrogen Sulfide
Cystathionine
Carbon Monoxide
Lyases
Oxygen
Nitric Oxide Synthase Type I
Phosphorylation
Heme
Cysteine
Reflex
Nitric Oxide
Respiration
Homeostasis
Gases
heme oxygenase-2

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Yuan, G., Vasavda, C., Peng, Y. J., Makarenko, V. V., Raghuraman, G., Nanduri, J., ... Prabhakar, N. R. (2015). Protein kinase G-regulated production of H2S governs oxygen sensing. Science Signaling, 8(373), [ra37]. https://doi.org/10.1126/scisignal.2005846

Protein kinase G-regulated production of H2S governs oxygen sensing. / Yuan, Guoxiang; Vasavda, Chirag; Peng, Ying Jie; Makarenko, Vladislav V.; Raghuraman, Gayatri; Nanduri, Jayasri; Gadalla, Moataz M.; Semenza, Gregg L; Kumar, Ganesh K.; Snyder, Solomon H; Prabhakar, Nanduri R.

In: Science Signaling, Vol. 8, No. 373, ra37, 21.04.2015.

Research output: Contribution to journalArticle

Yuan, G, Vasavda, C, Peng, YJ, Makarenko, VV, Raghuraman, G, Nanduri, J, Gadalla, MM, Semenza, GL, Kumar, GK, Snyder, SH & Prabhakar, NR 2015, 'Protein kinase G-regulated production of H2S governs oxygen sensing', Science Signaling, vol. 8, no. 373, ra37. https://doi.org/10.1126/scisignal.2005846
Yuan G, Vasavda C, Peng YJ, Makarenko VV, Raghuraman G, Nanduri J et al. Protein kinase G-regulated production of H2S governs oxygen sensing. Science Signaling. 2015 Apr 21;8(373). ra37. https://doi.org/10.1126/scisignal.2005846
Yuan, Guoxiang ; Vasavda, Chirag ; Peng, Ying Jie ; Makarenko, Vladislav V. ; Raghuraman, Gayatri ; Nanduri, Jayasri ; Gadalla, Moataz M. ; Semenza, Gregg L ; Kumar, Ganesh K. ; Snyder, Solomon H ; Prabhakar, Nanduri R. / Protein kinase G-regulated production of H2S governs oxygen sensing. In: Science Signaling. 2015 ; Vol. 8, No. 373.
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