| Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. | |
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MedLine Citation:
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PMID: 22245782 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Blood pressure regulation is crucial for the maintenance of health, and hypertension is a risk factor for myocardial infarction, heart failure, stroke and renal disease. Nitric oxide (NO) and prostacyclin trigger well-defined vasodilator pathways; however, substantial vasorelaxation in response to agents such as acetylcholine persists when the synthesis of these molecules is prevented. This remaining vasorelaxation activity, termed endothelium-derived hyperpolarizing factor (EDHF), is more prevalent in resistance than in conduit blood vessels and is considered a major mechanism for blood pressure control. Hydrogen peroxide (H(2)O(2)) has been shown to be a major component of EDHF in several vascular beds in multiple species, including in humans. H(2)O(2) causes the formation of a disulfide bond between the two α subunits of protein kinase G I-α (PKGI-α), which activates the kinase independently of the NO-cyclic guanosine monophosphate (cGMP) pathway and is coupled to vasodilation. To test the importance of PKGI-α oxidation in the EDHF mechanism and blood pressure control in vivo, we generated a knock-in mouse expressing only a C42S 'redox-dead' version of PKGI-α. This amino acid substitution, a single-atom change (an oxygen atom replacing a sulfur atom), blocked the vasodilatory action of H(2)O(2) on resistance vessels and resulted in hypertension in vivo. |
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Authors:
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Oleksandra Prysyazhna; Olena Rudyk; Philip Eaton |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-15 |
Journal Detail:
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Title: Nature medicine Volume: - ISSN: 1546-170X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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King's College London, Cardiovascular Division, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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