Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/185
Title: Role and Regulation of Colonic and Ileal Na-H Exchanger Isoforms-1 and -3 in Spontaneous Hypertensive Rats
Authors: Asma'a Ahmed اسماء احمد ابو غفره 
Supervisor: أ.د. اسلام خان
Keywords: Colonic and Ileal Na-H Exchanger Isoforms-1 and -3
Issue Date: 2012
Publisher:  Kuwait university - college of graduate studies
Abstract: Hypertension is associated with deregulation of several cation transporting mechanisms which maintain electrolyte and water homeostasis. Ileum and colon are key sites where absorption of electrolytes and water and other nutrients takes place with the help of several ion transporters including Na-H exchanger (NHE) isoforms-1 and -3. NHE performs water and electrolyte absorption from GI tract and has been shown to be induced in hypertension in several other tissues and cells. In this study we investigated a putative role of colonic and ileal NHE-1 and -3 isoforms and their regulatory factor NHERF using a 12-week old spontaneous hypertensive rat (SHR) model. cGK-II regulates anchoring of these isoforms to plasma membrane through ezrin with actin; therefore, levels of cGK-II were also examined. A group of SHR animals was treated with captopril (300 mg/L) starting from week 4 post birth and followed until week 12. Age-matched non-hypertensive genetic counterparts, WKY animals served as controls in this study. We also measured sodium pump activity which provides a driving force for NHE activity. Biochemical changes in the colon and ileum were examined by measuring myeloperoxidase activity (MPO). Localization of NHE-3 in lipid rafts is regulated through endocytosis and apical membrane recycling. The lipid raft membrane fractions were characterized using flotillin and caveolin markers, and by establishing profiles of cholesterol and total protein contents. SHR animals showed significant hypertension, proteinuria, renal and cardiac hypertrophy. In addition, there was a significant elevation in the MPO activity in ileum and colon in SHR. These changes were reversed by captopril treatment of SHR. Levels of NHE-1, NHE-3 and NHERF-1 protein expression were significantly decreased, while that of cGK-II was increased in SHR ileum and colon as compared to WKY controls. Except that there was a significant reversal of NHERF-1 levels, captopril was able to partially reverse these v changes in SHR. Sodium pump activity was also significantly decreased in both tissues and remained unaffected by captopril treatment of SHR. These changes do not seem to be due to any difference in the microsomal protein yield. Suppression of NHE-1 and -3 will negatively affect Na-dependent nutrient uptake and might cause cellular necrosis and Ca2+-mobilization that may support hypertension-induced damages in the GI tract. There was no significant change in the profile of NHE-1 and -3 between lipid raft membrane fractions, although the cholesterol profile was significantly different in SHR compared to WKY controls. These findings suggest that the NHE-1 and -3 isoforms are regulated by NHERF through induction of cGK-II. Earlier reports have shown increased activity of NHE in SHR jejunum, but there are no reports showing alteration in the NHE activity in ileum or colon which are the two most important organs where absorption of electrolyte occurs. We demonstrated evidence of mild inflammation in SHR colon and ileum due to hypertension. Suppression of NHE isoforms observed in our study might be a counteracting effect to increased blood pressure in SHR, whereas sodium pump suppression may lead to intracellular Na+ retention and cellular necrosis in the SHR intestine.
URI: http://hdl.handle.net/123456789/185
Appears in Programs:0540 Medical Biochemistry (M.Sc.)

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