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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  • 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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November 2012
Volume 30 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Xiao L, Lan A, Mo L, Xu W, Jiang N, Hu F, Feng J and Zhang C: 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. Int J Mol Med 30: 1126-1132, 2012.
APA
Xiao, L., Lan, A., Mo, L., Xu, W., Jiang, N., Hu, F. ... Zhang, C. (2012). 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. International Journal of Molecular Medicine, 30, 1126-1132. https://doi.org/10.3892/ijmm.2012.1090
MLA
Xiao, L., Lan, A., Mo, L., Xu, W., Jiang, N., Hu, F., Feng, J., Zhang, C."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". International Journal of Molecular Medicine 30.5 (2012): 1126-1132.
Chicago
Xiao, L., Lan, A., Mo, L., Xu, W., Jiang, N., Hu, F., Feng, J., Zhang, C."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". International Journal of Molecular Medicine 30, no. 5 (2012): 1126-1132. https://doi.org/10.3892/ijmm.2012.1090