About: Dissecting the role of renal folate metabolism in blood pressure regulation in spontaneously hypertensive rats     Goto   Sponge   NotDistinct   Permalink

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  • We will analyze the role of folate and sulfur amino acids in blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR). In preliminary linkage studies, we mapped a QTL for BP and plasma cysteine levels on chromosome 1 near the Folr1 (Folate receptor 1) candidate gene that plays an essential role in folate reabsortion in proximal tubules in the kidney. SHR Folr1 allele harbors a deletion in the promoter region that is associated with reduced renal expression and correlates inversely with BP. Linkage analyses were confirmed by testing SHR.BN-Folr1 congenic rats. In the current project, we will test the hypothesis that inherited variation in expression of Folr1 inside the kidney regulates BP through effects on intrarenal folate and homocysteine metabolism. We will use transgenic rescue experiments by expressing wild type Folr1 gene specifically in renal proximal tubules and investigate potential biochemical mechanisms whereby inherited variation in Folr1 expression inside the kidney promotes increased BP and risk for hypertension. (en)
  • Budeme analyzovat úlohu folátu a sirných aminokyselin při regulaci krevního tlaku (TK) u spontánně hypertenzních potkanů kmene SHR. V předběžných vazebných studiích jsme zmapovali QTL pro TK a plazmatický cystein na chromozom 1 blízko Folr1 (folátový receptor 1) kandidátního genu, který hraje klíčovou úlohu v reabsorpci folátu v proximálních tubulech ledvin. Folr1 alela kmene SHR nese deleci v promotoru, která je asociovaná se sníženou renální expresí a koreluje negatívně s TK. Vazebné analýzy byly potvrzeny testováním SHR.BN-Folr1 kongenních potkanů. V předkládaném projektu budeme testovat hypotézu, že geneticky podmíněná variabilita v intrarenální expresi Folr1 reguluje TK tím, jak ovlivňuje metabolizmus folátu a homocysteinu v ledvině. Použijeme komplementační experimenty s transgenní expresí Folr1 specificky v proximálních tubulech ledviny a budeme zkoumat možné biochemické mechanizmy, jimiž změněná intrarenální exprese Folr1 predisponuje kmen SHR k hypertenzi.
Title
  • Dissecting the role of renal folate metabolism in blood pressure regulation in spontaneously hypertensive rats (en)
  • Analýza úlohy renálního metabolizmu folátu při regulaci krevního tlaku u spontánně hypertenzních potkanů
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  • GA14-09283S
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  • sulfur amino acids, folate, blood pressure, spontaneously hypertensive rat (en)
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  • blood pressure
  • folate
  • sulfur amino acids
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