Hydrogen sulfide prevents hypoxia-induced apoptosis via inhibition of an H2O2-activated calcium signaling pathway in mouse hippocampal neurons
Hydrogen sulfide prevents hypoxia-induced apoptosis via inhibition of an H2O2-activated calcium signaling pathway in mouse hippocampal neurons
复制标题
硫化氢通过抑制小鼠海马神经元中 H2O2 激活的钙信号通路来防止缺氧诱导的细胞凋亡
DOI：
10.1016/j.bbrc.2012.07.131
复制
发表时间：
2012-08-24
影响因子：
3.1
通讯作者：
Yang, Xifei
中科院分区：
文献类型：
--
作者：
Luo, Yougen;Liu, Xiaoai;Yang, Xifei
硫化氢（H2S）是一种内源性气体介质，已被证明对各种刺激引起的人体不同器官的损伤具有保护作用。然而，H2S对缺氧诱导的神经元凋亡的影响及其机制尚不清楚。在这里，我们将小鼠海马神经元暴露于缺氧条件（2%O-2，5%CO2和93%N-2，37 ℃），以建立缺氧细胞模型。我们发现，4小时缺氧处理显着增加细胞内活性氧（ROS）水平，和预处理NaHS（H2S的来源）为30分钟抑制缺氧诱导的细胞内ROS的升高。缺氧处理显著增加细胞内[Ca ~（2+）]（i），NaHS预处理阻止[Ca ~（2+）]（i）的增加。此外，聚乙二醇（PEG）-过氧化氢酶（H2 O2清除剂），而不是PEG-SOD（O-2（-）清除剂）赋予类似H2S对缺氧诱导的[Ca 2 +]（i）增加的抑制作用。此外，我们发现NaHS预处理可显著抑制缺氧诱导的神经元凋亡，PEG-过氧化氢酶或1，4，5-三磷酸肌醇（IP 3）受体阻断剂xestospongin C也可抑制缺氧诱导的神经元凋亡。总之，这些研究结果表明，H2S抑制缺氧诱导的凋亡，通过抑制活性氧（主要是H2 O2）激活的钙信号通路在小鼠海马神经元。皇冠版权所有（c）2012由爱思唯尔公司发布。版权所有© 2016
Hydrogen sulfide (H2S), an endogenous gaseous mediator, has been shown to exert protective effects against damage to different organs in the human body caused by various stimuli. However, the potential effects of H2S on hypoxia-induced neuronal apoptosis and its mechanisms remain unclear. Here, we exposed mouse hippocampal neurons to hypoxic conditions (2% O-2, 5% CO2 and 93% N-2 at 37 degrees C) to establish a hypoxic cell model. We found that 4-h hypoxia treatment significantly increased intracellular reactive oxygen species (ROS) levels, and pretreatment with NaHS (a source of H2S) for 30 Min suppressed hypoxia-induced intracellular ROS elevation. The hypoxia treatment significantly increased cytosolic calcium ([Ca2+](i)), and pretreatment with NaHS prevented the increase in [Ca2+](i). Additionally, polyethylene glycol (PEG)-catalase (a H2O2 scavenger) but not PEG-SOD (an O-2(-) scavenger) conferred an inhibitory effect similar to H2S on the hypoxia-induced increase in [Ca2+](i). Furthermore, we found that pretreatment with NaHS could significantly inhibit hypoxia-induced neuronal apoptosis, which was also inhibited by PEG-catalase or the inositol 1,4,5-triphosphate (IP3) receptor blocker xestospongin C. Taken together, these findings suggest that H2S inhibits hypoxia-induced apoptosis through inhibition of a ROS (mainly H2O2)-activated Ca2+ signaling pathway in mouse hippocampal neurons. Crown Copyright (c) 2012 Published by Elsevier Inc. All rights reserved,