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

Xiao,Liangcan; Lan,Aiping; Mo,Liqiu; Xu,Wenming; Jiang,Nan; Hu,Fen; Feng,Jianqiang; Zhang,Changran

doi:10.3892/ijmm.2012.1090

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

Authors:
- Liangcan Xiao
- Aiping Lan
- Liqiu Mo
- Wenming Xu
- Nan Jiang
- Fen Hu
- Jianqiang Feng
- Changran Zhang
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China, Department of Internal Medicine, Region of Huangpu, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China
Published online on: August 8, 2012 https://doi.org/10.3892/ijmm.2012.1090
Pages: 1126-1132

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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.

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