• Yonghong Miao, Xiaoxue Sun, Guojun Gao, Xianglei Jia, Hao Wu, Ying Chen, and Liyong Huang.
• Department of Pediatrics, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.
• Toxicol In Vitro. 2019 Dec 1; 61: 104592.

Abstract(-)-epigallocatechin-3-gallate (EGCG), the main component of green tea, has long been explored in the treatment and/or prevention of central nervous system (CNS) disorders. However, EGCG has been recently shown to exhibit acute and subacute toxicity. Although a lot of work has been done, the mechanisms of EGCG-induced mitochondrial dysfunction has not been delineated in primary astrocyte. Here, the mitotoxic effect of EGCG on primary astrocytes was investigated by measuring Ca2+ overloading-induced mitochondrial dysfunction. As expected, EGCG dose-dependently inhibited astrocytes growth depending on Ca2+ overloading, especially at 50 μM EGCG group. It is interesting to note that Ca2+ influx from the extracellular space was responsible for an increase in the cytosolic Ca2+ level ([Ca2+]i) by opening voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca2+ ([Ca2+]m) overloaded via the mitochondrial Ca2+ uniporter (MCU). As a result, mitochondrial dysfunction was induced, including the opening of the mitochondrial permeability transition pore (mPTP), mitochondrial membrane depolarization, an increasing in reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Therefore, more apoptotic cells were observed in 50 μM EGCG group than that of in 1 μM EGCG group. These findings suggested that a high dose of EGCG was toxic to astrocytes partly by targeting mitochondria via calcium pathway, which would extend our understanding of the toxicity of EGCG and the underlying mechanisms.Copyright © 2019 Elsevier Ltd. All rights reserved.

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