title: Pdcd2l Promotes Palmitate-Induced Pancreatic Beta-Cell Apoptosis as a FoxO1 Target Gene.
abstract: Transcription factor FoxO1 is a key regulator of the insulin-signaling pathway, and is reported to play important roles in pancreatic β cell differentiation, proliferation, apoptosis and stress resistance. The multifunctional nature of FoxO1 is due to its regulation of various downstream targets. Previous studies in our lab identified potential FoxO1 target genes using the ChIP-DSL technique and one of those genes, Pdcd2l, was selected for further study. We found that the expression of Pdcd2l was increased with palmitate treatment; the luciferase assay result revealed that enhanced Pdcd2l promoter activity was responsible for the elevation of Pdcd2l expression. ChIP-PCR was performed to confirm the combination of FoxO1 to Pdcd2l promoter, result showing that FoxO1 could bind to Pdcd2l promoter and this binding was further enhanced after palmitate treatment. Overexpression of FoxO1 significantly induced Pdcd2l promoter activity, leading to increased mRNA level; consistently, interference of FoxO1 abolished the increment of Pdcd2l gene expression triggered by palmitate treatment. In addition, overexpression of Pdcd2l could further increase the percentage of apoptotic cells induced by palmitate incubation, whilst interference of Pdcd2l partially reversed the palmitate-induced apoptosis together with activated Caspase-3, indicating that the latter may play a part in this process. Therefore, in this study, we confirmed the binding of FoxO1 to the Pdcd2l gene promoter and studied the role of Pdcd2l in β cells for the first time. Our results suggested that FoxO1 may exert its activity partially through the regulation of Pdcd2l in palmitate-induced β cell apoptosis and could help to clarify the molecular mechanisms of β cell failure in type 2 diabetes.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.|Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yong
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.|Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lin
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.|Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000071161:Forkhead Box Protein O1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats
chemical_list: D002352:Carrier Proteins; D000071161:Forkhead Box Protein O1; C000620221:PDCD2L protein, human; D010168:Palmitates