Hydrogen sulfide protects PC12 cells against reactive oxygen species and extracellular signal-regulated kinase 1/2-mediated downregulation of glutamate transporter-1 expression induced by chemical hypoxia.

Abstract

Hypoxia and/or ischemia are implicated in neurodegenerative disorders. In these diseases, hypoxia/ischemia may induce oxidative stress, including production of reactive oxygen species (ROS), which result in a decrease in glutamate transporter expression. Hydrogen sulfide (H2S), as the third gasotransmitter, has neuroprotective effects and potent antioxidant properties. In the present study, we investigated the role of glutamate transporter-1 (GLT-1) in the protection of H2S against chemical hypoxia-induced injury in PC12 cells. We found that cobalt chloride (CoCl2), a chemical hypoxia agent, reduced the expression of GLT-1 in a time-dependent manner. Pretreatment with NaHS (a donor of H2S) reversed the CoCl2-induced downregulation of GLT-1 expression. Pretreatment with DHK (a selective inhibitor of GLT-1) for 30 min prior to NaHS preconditioning significantly inhibited the cytoprotection of H2S against CoCl2-induced injuries, leading to an increase in cytotoxicity and apoptosis as well as to a loss of mitochondrial membrane potential (MMP). In addition, we found that similar to the effect of NaHS, pretreatment with NAC (a ROS scavenger) or U0126 (a MEK1/2 inhibitor) blocked the downregulation of GLT-1 expression induced by CoCl2. Collectively, we demonstrated for the first time that ROS and extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated reduction of GLT-1 expression may be involved in chemical hypoxia-induced neural injury and that H2S attenuates this injury partly by upregulating GLT-1 expression in PC12 cells.

• Authors: Liangcan Xiao, Aiping Lan, Liqiu Mo, Wenming Xu, Nan Jiang, Fen Hu, Jianqiang Feng, Changran Zhang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 30 Issue 5 Pg. 1126-32 (Nov 2012) ISSN: 1791-244X [Electronic] Greece
• PMID: 22895544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Transporter 2
• Neuroprotective Agents
• Reactive Oxygen Species
• Cobalt
• dihydrokainic acid
• Extracellular Signal-Regulated MAP Kinases
• cobaltous chloride
• Kainic Acid
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis (drug effects)
• Cell Hypoxia (drug effects)
• Cell Survival (drug effects)
• Cobalt (pharmacology)
• Down-Regulation (drug effects)
• Excitatory Amino Acid Transporter 2 (antagonists & inhibitors, genetics, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism, physiology)
• Hydrogen Sulfide (pharmacology)
• Kainic Acid (analogs & derivatives, pharmacology)
• MAP Kinase Signaling System
• Neuroprotective Agents (pharmacology)
• PC12 Cells
• Rats
• Reactive Oxygen Species (metabolism)