PMID- 29446867 OWN - NLM STAT- MEDLINE DCOM- 20190122 LR - 20220124 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 62 IP - 8 DP - 2018 Apr TI - Epigallocatechin Gallate Reduces Amyloid beta-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis. PG - e1700890 LID - 10.1002/mnfr.201700890 [doi] AB - SCOPE: We investigated the role of endoplasmic reticulum (ER) stress in the protective effects of EGCG against the neuronal apoptosis in Abeta(1-42) -induced SH-SY5Y cells and APP/PS1 transgenic mice. METHODS AND RESULTS: Cell viability (CCK8 assay), flow cytometry, Hoechst 33258 staining, immunohistochemistry, transmission electron microscopy (TEM), and western blotting were used. EGCG prevented Abeta1-42-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. CONCLUSION: These 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. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Du, Ke AU - Du K AD - School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning, China. AD - Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. FAU - Liu, Mingyan AU - Liu M AD - School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning, China. AD - Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. FAU - Zhong, Xin AU - Zhong X AD - School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning, China. AD - Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. FAU - Yao, Weifan AU - Yao W AD - School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning, China. AD - Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. FAU - Xiao, Qinghuan AU - Xiao Q AD - School of Pharmacy, Department of Ion Channel Pharmacology, China Medical University, Shenyang, Liaoning, China. FAU - Wen, Quan AU - Wen Q AD - Shanghai Newsummit Biopharma Group, Zhangjiang Hi-Tech Park, Pudong District, Shanghai, China. FAU - Yang, Bo AU - Yang B AD - Shanghai Newsummit Biopharma Group, Zhangjiang Hi-Tech Park, Pudong District, Shanghai, China. FAU - Wei, Minjie AU - Wei M AD - School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning, China. AD - Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180323 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Amyloid beta-Peptides) RN - 0 (Ddit3 protein, mouse) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (HSPA5 protein, human) RN - 0 (Heat-Shock Proteins) RN - 0 (Hspa5 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Nootropic Agents) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-42)) RN - 147336-12-7 (Transcription Factor CHOP) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 3.4.22.- (Casp12 protein, mouse) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 12) RN - EC 3.4.22.- (Caspase 3) SB - IM EIN - Mol Nutr Food Res. 2022 Mar;66(5):e2270007. PMID: 35068066 MH - Alzheimer Disease/metabolism/pathology/prevention & control MH - Amyloid beta-Peptides/*antagonists & inhibitors/metabolism MH - Animals MH - *Apoptosis MH - Caspase 12/chemistry/genetics/metabolism MH - Caspase 3/chemistry/genetics/metabolism MH - Catechin/*analogs & derivatives/metabolism/therapeutic use MH - Cell Line, Tumor MH - Cell Survival MH - Cerebral Cortex/metabolism/pathology/ultrastructure MH - *Dietary Supplements MH - Endoplasmic Reticulum Chaperone BiP MH - *Endoplasmic Reticulum Stress MH - Heat-Shock Proteins/agonists/antagonists & inhibitors/genetics/metabolism MH - Humans MH - Mice, Transgenic MH - Microscopy, Electron, Transmission MH - Nerve Tissue Proteins/agonists/antagonists & inhibitors/genetics/metabolism MH - Neurons/*metabolism/pathology/ultrastructure MH - Neuroprotective Agents/*metabolism/therapeutic use MH - Nootropic Agents/metabolism/therapeutic use MH - Peptide Fragments/*antagonists & inhibitors/metabolism MH - Random Allocation MH - Transcription Factor CHOP/agonists/antagonists & inhibitors/genetics/metabolism OTO - NOTNLM OT - AD OT - EGCG OT - ER stress OT - green tea OT - neuronal apoptosis EDAT- 2018/02/16 06:00 MHDA- 2019/01/23 06:00 CRDT- 2018/02/16 06:00 PHST- 2017/10/24 00:00 [received] PHST- 2018/01/08 00:00 [revised] PHST- 2018/02/16 06:00 [pubmed] PHST- 2019/01/23 06:00 [medline] PHST- 2018/02/16 06:00 [entrez] AID - 10.1002/mnfr.201700890 [doi] PST - ppublish SO - Mol Nutr Food Res. 2018 Apr;62(8):e1700890. doi: 10.1002/mnfr.201700890. Epub 2018 Mar 23.