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Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways

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Abstract

Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.

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Acknowledgments

These studies were supported by the National Natural Science Foundation of China (Nos: 30770762, 30970987) to Dr. Xin-Yue Qin, a grant from the Health Department of Sichuan Province (No: 140032), and from the Doctoral Fund of affiliated hospital of Luzhou Medical College (No: 2014046) to Dr. Tao Tao.

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Authors and Affiliations

  1. Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 64600, Sichuan Province, China

    Tao Tao, Jie Fu & Xiao-gang Li

  2. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Jin-zhou Feng, Guang-hui Xu & Xin-yue Qin

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  1. Tao Tao
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  2. Jin-zhou Feng
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Correspondence to Xin-yue Qin.

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Tao, T., Feng, Jz., Xu, Gh. et al. Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways. Cell Mol Neurobiol 37, 417–426 (2017). https://doi.org/10.1007/s10571-016-0374-z

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