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Protein Kinase G Iα Oxidation Paradoxically Underlies Blood Pressure Lowering by the Reductant Hydrogen Sulfide.
MedLine Citation:
PMID:  25267801     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dysregulated blood pressure control leading to hypertension is prevalent and is a risk factor for several common diseases. Fully understanding blood pressure regulation offers the possibility of developing rationale therapies to alleviate hypertension and associated disease risks. Although hydrogen sulfide (H2S) is a well-established endogenous vasodilator, the molecular basis of its blood-pressure lowering action is incompletely understood. H2S-dependent vasodilation and blood pressure lowering in vivo was mediated by it catalyzing formation of an activating interprotein disulfide within protein kinase G (PKG) Iα. However, this oxidative activation of PKG Iα is counterintuitive because H2S is a thiol-reducing molecule that breaks disulfides, and so it is not generally anticipated to induce their formation. This apparent paradox was explained by H2S in the presence of molecular oxygen or hydrogen peroxide rapidly converting to polysulfides, which have oxidant properties that in turn activate PKG by inducing the disulfide. These observations are relevant in vivo because transgenic knockin mice in which the cysteine 42 redox sensor within PKG has been systemically replaced with a redox-dead serine residue are resistant to H2S-induced blood pressure lowering. Thus, a primary mechanism by which the reductant molecule H2S lowers blood pressure is mediated somewhat paradoxically by the oxidative activation of PKG.
Authors:
Daniel Stubbert; Oleksandra Prysyazhna; Olena Rudyk; Jenna Scotcher; Joseph R Burgoyne; Philip Eaton
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-29
Journal Detail:
Title:  Hypertension     Volume:  -     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-30     Completed Date:  -     Revised Date:  2014-10-1    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 American Heart Association, Inc.
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