Document Detail


Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries.
MedLine Citation:
PMID:  23172031     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study examined the role of the dual-specificity protein phosphatase-5 (DUSP-5) in the pressure-induced myogenic responses of organ-cultured cerebral arterial segments. In these studies, we initially compared freshly isolated and organ-cultured cerebral arterial segments with respect to responses to step increases in intravascular pressure, vasodilator and vasoconstrictor stimuli, activities of the large-conductance arterial Ca(2+)-activated K(+) (K(Ca)) single-channel current, and stable protein expression of DUSP-5 enzyme. The results demonstrate maintained pressure-dependent myogenic vasoconstriction, DUSP-5 protein expression, endothelium-dependent and -independent dilations, agonist-induced constriction, and unitary K(Ca) channel conductance in organ-cultured cerebral arterial segments similar to that in freshly isolated cerebral arteries. Furthermore, using a permeabilization transfection technique in organ-cultured cerebral arterial segments, gene-specific small interfering RNA (siRNA) induced knockdown of DUSP-5 mRNA and protein, which were associated with enhanced pressure-dependent cerebral arterial myogenic constriction and increased phosphorylation of PKC-βII. In addition, siRNA knockdown of DUSP-5 reduced levels of phosphorylated ROCK and ERK1 with no change in the level of phosphorylated ERK2. Pharmacological inhibition of ERK1/2 phosphorylation significantly attenuated pressure-induced myogenic constriction in cerebral arteries. The findings within the present studies illustrate that DUSP-5, native in cerebral arterial muscle cells, appears to regulate signaling of pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain.
Authors:
Nadi T Wickramasekera; Debebe Gebremedhin; Koryn A Carver; Padmanabhan Vakeel; Ramani Ramchandran; Aaron Schuett; David R Harder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-21
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  114     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-08-30     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  252-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / physiology
Cells, Cultured
Cerebral Arteries / cytology,  physiology*
Cerebrovascular Circulation / physiology*
Dual-Specificity Phosphatases / drug effects,  genetics,  physiology*
Male
Models, Animal
Muscle Development / physiology*
Muscle, Smooth, Vascular / cytology,  physiology*
Patch-Clamp Techniques
Potassium Channels, Calcium-Activated / physiology
RNA, Messenger / drug effects,  genetics
RNA, Small Interfering / pharmacology
Rats
Rats, Sprague-Dawley
Regional Blood Flow / physiology
Signal Transduction / physiology
Vasoconstriction / physiology*
Grant Support
ID/Acronym/Agency:
P01 HL-059996/HL/NHLBI NIH HHS; R01 HL-033833/HL/NHLBI NIH HHS; R01 HL-092105/HL/NHLBI NIH HHS; R01 HL-102745/HL/NHLBI NIH HHS; R01 HL-105997/HL/NHLBI NIH HHS; R01 HL033833/HL/NHLBI NIH HHS; R01 HL102745/HL/NHLBI NIH HHS; R01 HL105997/HL/NHLBI NIH HHS; T32 HL-007792/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Potassium Channels, Calcium-Activated; 0/RNA, Messenger; 0/RNA, Small Interfering; EC 3.1.3.48/Dual-Specificity Phosphatases; EC 3.1.3.48/Dusp5 protein, rat
Comments/Corrections

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