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Reduction in Autophagy by (-)-Epigallocatechin-3-Gallate (EGCG): a Potential Mechanism of Prevention of Mitochondrial Dysfunction After Subarachnoid Hemorrhage

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Abstract

Mitochondrial dysfunction and subsequent autophagy, which are common features in central nervous system (CNS) disorders, were found to contribute to neuronal cell injury after subarachnoid hemorrhage (SAH). (-)-Epigallocatechin-3-gallate (EGCG), the main biological active of tea catechin, is well known for its beneficial effects in the treatment of CNS diseases. Here, the ability of EGCG to rescue cellular injury and mitochondrial function following the improvement of autophagic flux after SAH was investigated. As expected, EGCG-protected mitochondrial function depended on the inhibition of cytosolic Ca2+ concentration ([Ca2+]i) influx via voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca2+ concentration ([Ca2+]m) overload via mitochondrial Ca2+ uniporter (MCU). The attenuated [Ca2+]i and [Ca2+]m levels observed in the EGCG-treated group likely lessened oxyhemoglobin (OxyHb)-induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization, mitochondrial membrane permeability transition pore (mPTP) opening, reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Subsequently, EGCG can restore the disrupted autophagy flux after SAH both at the initiation and formation stages by regulating Atg5, LC3B, and Becn-1 (Beclin-1) mRNA expressions. Thus, precondition EGCG resulted in autophagosomes and more autolysosomes compared with SAH group. As a result, EGCG pre-treatment increased the neurological score and decreased cell death. This study suggested that the mitochondrial dysfunction and abnormal autophagy flux synergistically contribute to SAH pathogenesis. Thus, EGCG can be regarded as a new pharmacological agent that targets both mitochondria and altered autophagy in SAH therapy.

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Authors and Affiliations

  1. College of Life Sciences, Henan Normal University, Xinxiang, Henan, 453007, China

    Ying Chen

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

    Liyong Huang, Xiling Diao, Shuyang Zhao & Wenke Zhou

  3. College of Life Science and Biotechnology, Xinxiang Medical University, Xinxiang, Henan, 453003, China

    Huiyong Zhang

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Correspondence to Ying Chen.

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This work is supported by the National Nature Sciences Foundation of China (No. 31200519) and Natural Science Foundation of Henan (No. 132300410339).

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Chen, Y., Huang, L., Zhang, H. et al. Reduction in Autophagy by (-)-Epigallocatechin-3-Gallate (EGCG): a Potential Mechanism of Prevention of Mitochondrial Dysfunction After Subarachnoid Hemorrhage. Mol Neurobiol 54, 392–405 (2017). https://doi.org/10.1007/s12035-015-9629-9

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