Gaseous messengers in oxygen sensing.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
N R Prabhakar, Gregg L Semenza

Abstract

The carotid body is a sensory organ that detects acute changes in arterial blood oxygen (O(2)) levels and reflexly mediates systemic cardiac, vascular, and respiratory responses to hypoxia. This article provides a brief update of the roles of gas messengers as well as redox homeostasis by hypoxia-inducible factors (HIFs) in hypoxic sensing by the carotid body. Carbon monoxide (CO) and nitric oxide (NO), generated by heme oxygenase-2 (HO-2) and neuronal nitric oxide synthase (nNOS), respectively, inhibit carotid body activity. Molecular O(2) is a required substrate for the enzymatic activities of HO-2 and nNOS. Stimulation of carotid body activity by hypoxia may reflect reduced formation of CO and NO. Glomus cells, the site of O(2) sensing in the carotid body, express cystathionine γ-lyase (CSE), an H(2)S generating enzyme. Cth ( -/- ) mice, which lack CSE, exhibit severely impaired hypoxia-induced H(2)S generation, sensory excitation, and stimulation of breathing in response to low O(2). Hypoxia-evoked H(2)S generation in the carotid body requires the interaction of CSE with HO-2, which generates CO. Carotid bodies from Hif1a ( +/- ) mice with partial HIF-1α deficiency do not respond to hypoxia, whereas carotid bodies from mice...Continue Reading

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Citations

Feb 22, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gregg L Semenza, Nanduri R Prabhakar
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