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Nitric Oxide. 2018 Jun 1;76:97-104. doi: 10.1016/j.niox.2018.03.013. Epub 2018 Mar 22.

Redox regulation of soluble guanylyl cyclase.

Author information

1
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
2
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: astraub@pitt.edu.

Abstract

The nitric oxide/soluble guanylyl cyclase (NO-sGC) signaling pathway regulates the cardiovascular, neuronal, and gastrointestinal systems. Impaired sGC signaling can result in disease and system-wide organ failure. This review seeks to examine the redox control of sGC through heme and cysteine regulation while discussing therapeutic drugs that target various conditions. Heme regulation involves mechanisms of insertion of the heme moiety into the sGC protein, the molecules and proteins that control switching between the oxidized (Fe3+) and reduced states (Fe2+), and the activity of heme degradation. Modifications to cysteine residues by S-nitrosation on the α1 and β1 subunits of sGC have been shown to be important in sGC signaling. Moreover, redox balance and localization of sGC is thought to control downstream effects. In response to altered sGC activity due to changes in the redox state, many therapeutic drugs have been developed to target decreased NO-sGC signaling. The importance and relevance of sGC continues to grow as sGC dysregulation leads to numerous disease conditions.

KEYWORDS:

Heme; Localization; Redox; Soluble guanylyl cyclase; Therapeutics; Thiol

PMID:
29578056
PMCID:
PMC5916318
DOI:
10.1016/j.niox.2018.03.013
[Indexed for MEDLINE]
Free PMC Article

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