Epigallocatechin Gallate Reduces Amyloid β-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.
Epigallocatechin Gallate Reduces Amyloid β-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.
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表没食子儿茶素没食子酸酯通过抑制内质网应激介导的细胞凋亡来减少淀粉样蛋白 β 诱导的神经毒性。
DOI：
10.1002/mnfr.202270007
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发表时间：
2022-01
影响因子：
5.2
通讯作者：
Minjie Wei
中科院分区：
文献类型：
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作者：
Ke Du;Mingyan Liu;Xin Zhong;Weifan Yao;Qinghuan Xiao;Quan Wen;Bo Yang;Minjie Wei
范围我们研究了内质网（ER）应激在EGCG对Aβ1-42诱导的SH-SY5Y细胞和APP/PS1转基因小鼠神经元凋亡的保护作用中的作用。方法和结果细胞活力（CCK8测定）、流式细胞术、Hoechst 33258染色、免疫组化、透射电子 使用显微镜（TEM）和蛋白质印迹法。 EGCG 以剂量依赖性方式阻止 Aβ1-42 诱导的 SH-SY5Y 细胞毒性、增加细胞活力并减少细胞凋亡。在随后的机制研究中，发现这种作用导致 GRP78、CHOP、cleaved-caspase-12 和 ‐3 的下调。此外，EGCG 还降低了两种 ER 应激激活剂衣霉素 (TM) 和毒胡萝卜素 (TG) 诱导的细胞毒性。与体外研究一致，EGCG 抑制 APP/PS1 转基因小鼠皮质中的神经元凋亡，减轻 ER 异常超微结构肿胀和下调 ER 应激相关蛋白。结论这些结果表明 EGCG 通过一种新机制减轻阿尔茨海默病 (AD) 的神经毒性： 涉及在体外和体内抑制 ER 应激相关神经元凋亡，这表明 EGCG 在 AD 营养预防策略中具有巨大潜力。
ScopeWe investigated the role of endoplasmic reticulum (ER) stress in the protective effects of EGCG against the neuronal apoptosis in Aβ1‐42‐induced SH‐SY5Y cells and APP/PS1 transgenic mice.Methods and resultsCell viability (CCK8 assay), flow cytometry, Hoechst 33258 staining, immunohistochemistry, transmission electron microscopy (TEM), and western blotting were used. EGCG prevented Aβ1‐42‐induced toxicity in SH‐SY5Y cells, increased cell viability, and decreased apoptosis in a dose‐dependent manner. In a subsequent mechanism study, it was found that this effect contributed to the down‐regulation of GRP78, CHOP, cleaved‐caspase‐12 and ‐3. Moreover, EGCG also reduced the cytotoxicity induced by tunicamycin (TM) and thapsigargin (TG), two ER stress activators. Consistent with the in vitro study, EGCG inhibited neuronal apoptosis in the cortex of APP/PS1 transgenic mice, with the mitigation of ER abnormal ultrastructural swelling and the downregulation of ER‐stress‐associated proteins.ConclusionThese results indicate that EGCG attenuates the neurotoxicity in Alzheimer's disease (AD) via a novel mechanism that involves inhibition of ER‐stress‐associated neuronal apoptosis in vitro and in vivo, suggesting the tremendous potential of EGCG for use in a nutritional preventive strategy against AD.