Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a n...Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.展开更多
Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cot...Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cotransporter （ NCC）, and the Cl^- channel （ CLC ）-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2.Methods Sprague Dawleys rats were treated subcutaneously with either Ang Ⅱ （100 ng·kg^-1·min^-1） or vehicle for 14 days. Expression of NKCC2, NCC and CLC-K2 mRNA in kidneys was determined by real time polymerase chain reaction （PCR）. Western blotting analysis was used to measure NKCC2 and NCC protein expression.Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold （P 〈 0.05 ） . There were no changes in NCC mRNA or protein expression in AngⅡ-treated rats versus control.Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na^＋ and Cl^- reabsorption in response to Ang Ⅱ.展开更多
文摘Gitelman's syndrome(GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazidesensitive Na Cl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyperreninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation(c.2581 C > T) and a new one(c.283 del C) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stopcodon(pG ln95 Argfs X19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.
文摘Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cotransporter （ NCC）, and the Cl^- channel （ CLC ）-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2.Methods Sprague Dawleys rats were treated subcutaneously with either Ang Ⅱ （100 ng·kg^-1·min^-1） or vehicle for 14 days. Expression of NKCC2, NCC and CLC-K2 mRNA in kidneys was determined by real time polymerase chain reaction （PCR）. Western blotting analysis was used to measure NKCC2 and NCC protein expression.Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold （P 〈 0.05 ） . There were no changes in NCC mRNA or protein expression in AngⅡ-treated rats versus control.Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na^＋ and Cl^- reabsorption in response to Ang Ⅱ.
