Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel.
Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel.
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DOI：
10.1155/2015/976848
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发表时间：
2015
影响因子：
--
通讯作者：
Ma HP
中科院分区：
文献类型：
--
作者：
Wang Q;Song B;Jiang S;Liang C;Chen X;Shi J;Li X;Sun Y;Wu M;Zhao D;Zhang ZR;Ma HP
晚期糖基化终产物（AGEs）是一种复杂的异质性化合物，与糖尿病有关。通过远端肾单位上皮钠通道（ENaC）的钠重吸收在糖尿病高血压中起重要作用。在这里，我们报告，H2S拮抗AGEs诱导的ENaC激活A6细胞。外源AGEs可显著增加A6细胞ENaC开放概率（PO），而NaHS（H2S供体）和TEMPO可阻断AGEs诱导的ENaC活性。与过氧化氢酶抑制剂3-氨基三唑（3-AT）孵育A6细胞模拟AGEs对ENaC活性的影响，但没有诱导任何累加效应。我们发现，过氧化氢酶的表达水平显着降低AGEs和3-AT促进A6细胞的ROS摄取，这是显着抑制NaHS。特异性PTEN和PI 3 K抑制剂BPV（pic）和LY 294002影响AGEs预处理的A6细胞中的ENaC活性。AGEs预处理A6细胞72小时后，ENaC PO仍维持在较高水平，提示AGEs相关的“代谢记忆”可能参与了钠稳态的调节。我们的数据首次表明，H2S通过靶向ROS/PI 3 K/PTEN途径阻止AGEs诱导的ENaC活化。
Advanced glycation end-products (AGEs) are complex and heterogeneous compounds implicated in diabetes. Sodium reabsorption through the epithelial sodium channel (ENaC) at the distal nephron plays an important role in diabetic hypertension. Here, we report that H2S antagonizes AGEs-induced ENaC activation in A6 cells. ENaC open probability (P O) in A6 cells was significantly increased by exogenous AGEs and that this AGEs-induced ENaC activity was abolished by NaHS (a donor of H2S) and TEMPOL. Incubating A6 cells with the catalase inhibitor 3-aminotriazole (3-AT) mimicked the effects of AGEs on ENaC activity, but did not induce any additive effect. We found that the expression levels of catalase were significantly reduced by AGEs and both AGEs and 3-AT facilitated ROS uptake in A6 cells, which were significantly inhibited by NaHS. The specific PTEN and PI3K inhibitors, BPV(pic) and LY294002, influence ENaC activity in AGEs-pretreated A6 cells. Moreover, after removal of AGEs from AGEs-pretreated A6 cells for 72 hours, ENaC P O remained at a high level, suggesting that an AGEs-related “metabolic memory” may be involved in sodium homeostasis. Our data, for the first time, show that H2S prevents AGEs-induced ENaC activation by targeting the ROS/PI3K/PTEN pathway.
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DOI：
10.1124/jpet.105.092023
发表时间：
2006-02-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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4.2
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