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Involvement of ERK1/2 Pathway in Neuroprotection by Salidroside Against Hydrogen Peroxide-Induced Apoptotic Cell Death

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Abstract

Salidroside is isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has a potent antioxidant property. The aim of this study was to investigate the effects of salidroside on hydrogen peroxide (H2O2)-induced cell apoptosis in nerve growth factor (NGF)-differentiated PC12 cells and the possible involvement of the extracellular signal-related protein kinase 1/2 (ERK1/2) signaling pathway. MTT assay, Hoechst 33342 staining, and TdT-mediated dUTP-biotin nick end labeling assay collectively showed that pretreatment with salidroside alleviated, in a dose-dependent manner, cell viability loss and apoptotic cell death induced by H2O2 stimulation in cultured NGF-differentiated PC12 cells. According to Western blot analysis, pretreatment with salidroside transiently caused the activation of ERK1/2 pathway; a selective inhibitor of the mitogen-activated protein kinase kinase (MAPKK, MEK) blocked salidroside-activated ERK pathway and thus attenuated the influences of salidroside on H2O2-induced increase in the level of cleaved caspase-3, a chief executant of apoptosis cascades. Morphological analysis further indicated that in the presence of the MEK inhibitor, the neuroprotective effect of salidroside against H2O2-evoked cell apoptosis was significantly abrogated. Taken together, the results suggest that the neuroprotective effects of salidroside might be modulated by ERK signaling pathway, especially at the level or upstream of the caspase-3 activation.

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Acknowledgements

This study was supported by Hi-Tech Research and Development Program of China (973 Program, Grant No. 2003CB515306).

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  1. Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, People’s Republic of China

    Shu Yu, Yuntian Shen, Jie Liu & Fei Ding

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  1. Shu Yu
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Correspondence to Fei Ding.

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Yu, S., Shen, Y., Liu, J. et al. Involvement of ERK1/2 Pathway in Neuroprotection by Salidroside Against Hydrogen Peroxide-Induced Apoptotic Cell Death. J Mol Neurosci 40, 321–331 (2010). https://doi.org/10.1007/s12031-009-9292-6

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