title: Epigallocatechin-3-Gallate Inhibits Ethanol-Induced Apoptosis Through Neurod1 Regulating CHOP Expression in Pancreatic β-Cells.
abstract: Epiga-llocatechin-3-gallate (EGCG) is one kind of polyphenol abundant extracted from green tea which has a potent antidiabetic activity. However, the molecular mechanisms mediating the protection procession of EGCG are still unclear. The aim of this study was to investigate the protective effect of EGCG on pancreatic β-cells exposed to ethanol and the possible underlying mechanisms. To observe the effect of EGCG, we assessed apoptosis in βTC-6 and INS-1 cells, which were in complete medium containing 60 mM ethanol, or coincubation with different concentration of EGCG. We also evaluated the roles of Neurod1 in CHOP expression and ethanol-mediated damage through plasmid overexpression. Treatment with EGCG decreased CHOP expression and apoptosis, whereas its treatment increased Neurod1 expression in ethanol-treated βTC-6 and INS-1 cells. Overexpression of Neurod1 caused the decrease of CHOP expression and apoptosis in ethanol-treated cells. Furthermore, Neurod1 inhibited CHOP expression by deacetylation of Histone H4 at the CHOP gene promoter. In addition, EGCG partially restores the activity of Neurod1 binding to CHOP promoter in ethanol-treated cells. In conclusion, EGCG protected β-cell against ethanol-induced β-cell apoptosis by Neurod1 regulating CHOP expression.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Tijun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shan
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002392:Catechin; D002492:Central Nervous System Depressants; D000431:Ethanol; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; C093564:Neurogenic differentiation factor 1; C045651:epigallocatechin gallate
keywords: CHOP; EGCG; Neurod1; ethanol; β-cells