Hydrogen sulfide prevents hydrogen peroxide-induced activation of epithelial sodium channel through a PTEN/PI(3,4,5)P3 dependent pathway.
Hydrogen sulfide prevents hydrogen peroxide-induced activation of epithelial sodium channel through a PTEN/PI(3,4,5)P3 dependent pathway.
复制标题
DOI：
10.1371/journal.pone.0064304
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhang J;Chen S;Liu H;Zhang B;Zhao Y;Ma K;Zhao D;Wang Q;Ma H;Zhang Z
通过肾脏远端上皮性钠通道(ENaC)的钠重吸收在盐敏感型高血压中起重要作用。我们先前报道，过氧化氢(H_2O_2)通过升高A6远端肾单位细胞顶膜磷脂酰肌醇3，4，5-三磷酸(PI(3，4，5)P3)来刺激ENaC。在这里，我们报告了H_2S可以拮抗H_2O_2诱导的A6细胞ENaC的激活。我们的细胞附着式膜片钳数据显示，外源H_2O_2显著增加了ENaC的开放概率(PO)，这与我们之前的发现一致。外源性H_2O_2诱导的ENaC的异常激活可被H_2S(0.1 mM NaHS)完全消除。H_2S处理A6细胞后，ENaC-PO略有下降，但H_2O_2不能使ENaC-PO升高。共聚焦显微镜数据显示，外源H_2O_2作用于A6细胞后，细胞内ROS水平显著升高，PI(3，4，5)P3在细胞膜顶端积聚。外源H_2O_2对A6细胞内ROS水平和细胞顶端PI(3，4，5)P3水平的影响可被H_2S几乎完全消除。此外，H_2S显著抑制H_2O_2诱导的肿瘤抑制蛋白磷酸酶和张力蛋白同源酶(PTEN)的氧化失活，PTEN是PI(3，4，5)P3的负调节因子。此外，PTEN的特异性抑制剂BPV(Pic)可提高A6细胞PI(3，4，5)P3和ENaC的活性，其作用方式与H_2O_2类似。我们的数据首次表明，H_2S通过PTEN-PI(3，4，5)P3依赖的途径抑制H_2O_2诱导的ENaC的激活。
Sodium reabsorption through the epithelial sodium channel (ENaC) at the distal segment of the kidney plays an important role in salt-sensitive hypertension. We reported previously that hydrogen peroxide (H2O2) stimulates ENaC in A6 distal nephron cells via elevation of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) in the apical membrane. Here we report that H2S can antagonize H2O2-induced activation of ENaC in A6 cells. Our cell-attached patch-clamp data show that ENaC open probability (PO) was significantly increased by exogenous H2O2, which is consistent with our previous finding. The aberrant activation of ENaC induced by exogenous H2O2 was completely abolished by H2S (0.1 mM NaHS). Pre-treatment of A6 cells with H2S slightly decreased ENaC PO; however, in these cells H2O2 failed to elevate ENaC PO. Confocal microscopy data show that application of exogenous H2O2 to A6 cells significantly increased intracellular reactive oxygen species (ROS) level and induced accumulation of PI(3,4,5)P3 in the apical compartment of the cell membrane. These effects of exogenous H2O2 on intracellular ROS levels and on apical PI(3,4,5)P3 levels were almost completely abolished by treatment of A6 cells with H2S. In addition, H2S significantly inhibited H2O2-induced oxidative inactivation of the tumor suppressor phosphatase and tensin homolog (PTEN) which is a negative regulator of PI(3,4,5)P3. Moreover, BPV(pic), a specific inhibitor of PTEN, elevated PI(3,4,5)P3 and ENaC activity in a manner similar to that of H2O2 in A6 cells. Our data show, for the first time, that H2S prevents H2O2-induced activation of ENaC through a PTEN-PI(3,4,5)P3 dependent pathway.
登录
查看更多内容
影响因子：
5.5
作者：
Blazer-Yost, BL;Vahle, JC;Bacallao, RL
通讯作者：
Bacallao, RL
影响因子：
2.2
作者：
Henderson, Peter W.;Singh, Sunil P.;Spector, Jason A.
通讯作者：
Spector, Jason A.
DOI：
10.1124/jpet.105.092023
发表时间：
2006-02-01
影响因子：
3.5
作者：
Bian, JS;Yong, QC;Moore, PK
通讯作者：
Moore, PK
影响因子：
4.8
作者：
Lee, SR;Yang, KS;Rhee, SG
通讯作者：
Rhee, SG
影响因子：
4.8
作者：
Kimura, Y;Kimura, H
通讯作者：
Kimura, H