Hydrogen sulfide prevents hypoxia-induced apoptosis via inhibition of an H2O2-activated calcium signaling pathway in mouse hippocampal neurons.

Abstract

Hydrogen sulfide (H(2)S), 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 H(2)S on hypoxia-induced neuronal apoptosis and its mechanisms remain unclear. Here, we exposed mouse hippocampal neurons to hypoxic conditions (2% O(2), 5% CO(2) and 93% N(2) at 37 °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 H(2)S) for 30 min suppressed hypoxia-induced intracellular ROS elevation. The hypoxia treatment significantly increased cytosolic calcium ([Ca(2+)](i)), and pretreatment with NaHS prevented the increase in [Ca(2+)](i). Additionally, polyethylene glycol (PEG)-catalase (a H(2)O(2) scavenger) but not PEG-SOD (an O(2)(-) scavenger) conferred an inhibitory effect similar to H(2)S on the hypoxia-induced increase in [Ca(2+)](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 (IP(3)) receptor blocker xestospongin C. Taken together, these findings suggest that H(2)S inhibits hypoxia-induced apoptosis through inhibition of a ROS (mainly H(2)O(2))-activated Ca(2+) signaling pathway in mouse hippocampal neurons.

• Authors: Yougen Luo, Xiaoai Liu, Qisheng Zheng, Xiaomei Wan, Shuichang Ouyang, Yedong Yin, Xiaojing Sui, Jianjun Liu, Xifei Yang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 425 Issue 2 Pg. 473-7 (Aug 24 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22846576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Chemical References

• Macrocyclic Compounds
• Oxazoles
• Reactive Oxygen Species
• catalase-polyethylene glycol
• xestospongin C
• Polyethylene Glycols
• Hydrogen Peroxide
• Catalase
• Calcium
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis
• Calcium (metabolism)
• Calcium Signaling
• Catalase (metabolism)
• Cell Hypoxia
• Cells, Cultured
• Hippocampus (metabolism, physiology)
• Hydrogen Peroxide (pharmacology)
• Hydrogen Sulfide (metabolism)
• Macrocyclic Compounds (metabolism)
• Mice
• Mice, Inbred BALB C
• Neurons (cytology, metabolism, physiology)
• Oxazoles (metabolism)
• Polyethylene Glycols (metabolism)
• Reactive Oxygen Species (metabolism)