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p38 Inhibitor Protects Mitochondrial Dysfunction by Induction of DJ-1 Mitochondrial Translocation After Subarachnoid Hemorrhage

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Abstract

p38 mitogen-activated protein kinase (MAPK) is a major player in mitochondrial dysfunction after subarachnoid hemorrhage (SAH). Moreover, DJ-1, which responds to oxidative stress and translocates to mitochondria, maintains mitochondrial homeostasis. Although a few studies have demonstrated that DJ-1 indirectly regulates p38 activation, the relationship between DJ-1 and p38 in mitochondrial dysfunction after SAH has not been delineated. Using an in vitro SAH model, alterations in p38, p-p38, DJ-1, and autophagic-related protein expression were detected. As expected, p38 inhibitor significantly blocked excessive expression of p38 and p-p38 after SAH, whereas total DJ-1 expression and mitochondrial DJ-1 were up-regulated. Further analysis showed that p38 inhibitor significantly blocked oxyhemoglobin (OxyHb) induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. In addition, p38 inhibitor restored OxyHb-induced abnormal autophagic flux at the initiation and formation stage by regulating Atg5, beclin-1, the ratio of LC3-II/LC3-I, and p62 expression. This study suggested that overexpression of p38 induced the accumulation of mitochondrial dysfunction partly due to abnormal activation of autophagy, which largely relied on DJ-1 mitochondrial translocation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81541030) and Henan Province of Natural Science Foundation (No. 182300410299).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China

    Liyong Huang, Yaqing Hou, Lei Wang, Xiahui Xu, Qingkai Guan, Xiangsheng Li & Wenke Zhou

  2. College of Life Science, Henan Normal University, Xinxiang, 453007, Henan, China

    Ying Chen

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  1. Liyong Huang
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  2. Yaqing Hou
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  3. Lei Wang
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  4. Xiahui Xu
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  7. Ying Chen
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  8. Wenke Zhou
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Correspondence to Wenke Zhou.

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Huang, L., Hou, Y., Wang, L. et al. p38 Inhibitor Protects Mitochondrial Dysfunction by Induction of DJ-1 Mitochondrial Translocation After Subarachnoid Hemorrhage. J Mol Neurosci 66, 163–171 (2018). https://doi.org/10.1007/s12031-018-1131-1

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  • DOI: https://doi.org/10.1007/s12031-018-1131-1

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