Zhao Xiaoling, Li Renjia, Jin Hui, Jin Haimin, Wang Yonghui, Zhang Wanqi, Wang Haichao, Chen Weiqiang
Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
Tianjin Medical University, Tianjin, China.
PLoS One. 2018 Jan 26;13(1):e0192083. doi: 10.1371/journal.pone.0192083. eCollection 2018.
Extensive studies suggested epigallocatechin-3-gallate (EGCG) has significant neuroprotection against multiple central neural injuries, but the underlying mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase/ protein kinase B (PI3K/AKT) pathways in EGCG-mediated protection against corticosterone-induced neuron injuries. As an essential stress hormone, corticosterone could induce obvious neurotoxicity in primary hippocampal neurons. Pre-treatment with EGCG ameliorated the corticosterone-induced neuronal injuries; however, it was blocked by pharmacological inhibitors for ERK1/2 (U0126) and PI3K/AKT (LY294002). Furthermore, the results confirmed that EGCG restored the corticosterone-induced decrease of ERK1/2 and PI3K/AKT phosphorylation, and attenuated the corticosterone-induced reduction of peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) expression and ATP production. Taken together, these findings indicated that EGCG has significant neuroprotection against corticosterone-induced neuron injuries partly via restoring the ERK1/2 and PI3K/AKT signaling pathways as well as the PGC-1α-mediated ATP production.
大量研究表明，表没食子儿茶素-3-没食子酸酯（EGCG）对多种中枢神经损伤具有显著的神经保护作用，但其潜在机制仍未完全阐明。在此，我们提供证据支持细胞外信号调节激酶1/2（ERK1/2）和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）信号通路可能参与EGCG介导的对皮质酮诱导的神经元损伤的保护作用。作为一种重要的应激激素，皮质酮可在原代海马神经元中诱导明显的神经毒性。EGCG预处理可改善皮质酮诱导的神经元损伤；然而，ERK1/2的药理学抑制剂（U0126）和PI3K/AKT的药理学抑制剂（LY294002）可阻断这种保护作用。此外，结果证实EGCG可恢复皮质酮诱导的ERK1/2和PI3K/AKT磷酸化水平的降低，并减轻皮质酮诱导的过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）表达和ATP生成的减少。综上所述，这些发现表明，EGCG对皮质酮诱导的神经元损伤具有显著的神经保护作用，部分是通过恢复ERK1/2和PI3K/AKT信号通路以及PGC-1α介导的ATP生成来实现的。
