Document Detail


Renal expression of arachidonic acid metabolizing enzymes and RhoA/Rho kinases in fructose insulin resistant hypertensive rats.
MedLine Citation:
PMID:  19633817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fructose feeding has been shown to induce insulin resistance and hypertension. Renal protein expression for the cytochrome P (CYP) 450 arachidonic acid metabolizing enzymes has been shown to be altered in other models of diet-induced hypertension. Of special interest is CYP4A, which produces the potent vasoconstrictor, 20-hydroxyeicosatetraenoic acid and CYP2C, which catalyzes the formation of the potent dilators epoxyeicosatrienoic acids as well as soluble epoxide hydrolase (sEH) which metabolizes the latter to dihydroxyeicosatrienoic acids. The RhoA/Rho kinase (ROCK) signaling pathway is downstream of arachidonic acid and is reported to mediate metabolic-cardio-renal dysfunctions in some experimental models of insulin resistance and diabetes. The aim of the present study was to determine the expression of CYP4A, CYP2C23, CYP2C11, sEH, RhoA, ROCK-1, ROCK-2, and phospho-Lin-11/Isl-1/Mec-3 kinase (LIMK) in kidneys of fructose-fed (F) rats. Male Wistar rats were fed a high fructose diet for 8 weeks. Body weight, systolic blood pressure, insulin sensitivity, and renal expression of the aforementioned proteins were assessed. No change was observed in the body weight of F rats; however, euglycemia and hyperinsulinemia implicating impaired glucose tolerance and significant elevation in systolic blood pressure were observed. Renal expression of CYP4A and CYP2C23 was significantly increased while that of CYP2C11 and sEH was not changed in F rats. Equal expression for RhoA in both control and F rats and an enhanced level of ROCK-1 and ROCK-2 constitutively activate 130 kDa cleavage fragments as well as phospho-LIMK. These data suggest that the kidneys could be actively participating in the pathogenesis of insulin resistance-induced hypertension through the arachidonic acid CYP 450-RhoA/Rho kinase pathway(s).
Authors:
Sally Mustafa; Harish Vasudevan; Violet G Yuen; John H McNeill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-25
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  333     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  203-9     Citation Subset:  IM    
Affiliation:
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.
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MeSH Terms
Descriptor/Qualifier:
Alkane 1-Monooxygenase / analysis
Animals
Arachidonic Acid / metabolism
Aryl Hydrocarbon Hydroxylases / analysis
Cytochrome P-450 Enzyme System / analysis*,  biosynthesis
Fructose / administration & dosage,  pharmacology
Hypertension / chemically induced,  enzymology*,  metabolism
Insulin Resistance*
Kidney / enzymology*,  metabolism
Lim Kinases / analysis,  biosynthesis
Male
Rats
Rats, Wistar
Steroid 16-alpha-Hydroxylase / analysis
rho-Associated Kinases / analysis*,  biosynthesis
Chemical
Reg. No./Substance:
30237-26-4/Fructose; 506-32-1/Arachidonic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C11 protein, rat; EC 1.14.14.1/Steroid 16-alpha-Hydroxylase; EC 1.14.14.1/arachidonate epoxygenase; EC 1.14.15.3/Alkane 1-Monooxygenase; EC 2.7.11.1/Lim Kinases; EC 2.7.11.1/rho-Associated Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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