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Author Notes:

Email Address: Zhi-Ren Zhang: zhirenz@yahoo.com He-Ping Ma:heping.ma@emory.edu

Qiushi Wang and Binlin Song contributed equally to this work.

The authors have no conflict of interests to declare.


Research Funding:

Key Project of Chinese National Program for Fundamental Research and Development (973 Program 2012CB517803, 2014CB542401 to Zhi-Ren Zhang)

National Natural Science Foundation of China (81070217, 81270340, and 81320108002 to Zhi-Ren Zhang)

National Institutes of Health grant (R01 DK 100582 to He-Ping Ma)

Research Project of Health and Family Planning Commission of Heilongjiang Province (2014-330 to Binlin Song)

Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel.

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Journal Title:

Oxidative Medicine and Cellular Longevity


Volume 2015


, Pages 976848-976848

Type of Work:

Article | Final Publisher PDF


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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© 2015 Qiushi Wang et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits making multiple copies, distribution of derivative works, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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