ArticleDiabetologia2012
Identification of direct forkhead box O1 targets involved in palmitate-induced apoptosis in clonal insulin-secreting cells using chromatin immunoprecipitation coupled to DNA selection and ligation.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 28 citations in OpenAlex.
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- Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation.Diabetologia · 2020Article
- Long noncoding RNA Gomafu upregulates Foxo1 expression to promote hepatic insulin resistance by sponging miR-139-5p.Cell death & disease · 2018Article
- Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.PloS one · 2017Article
- TRPM2 regulates TXNIP-mediated NLRP3 inflammasome activation via interaction with p47 phox under high glucose in human monocytic cells.Scientific reports · 2016Article
- Clinical significance and functional validation of PPA1 in various tumors.Cancer medicine · 2016Article
- A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice.Diabetologia · 2016Article
- Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models.Diabetologia · 2016Article
- Pdcd2l Promotes Palmitate-Induced Pancreatic Beta-Cell Apoptosis as a FoxO1 Target Gene.PloS one · 2016Article
- Aldosterone induces clonal β-cell failure through glucocorticoid receptor.Scientific reports · 2015Article
- Foxc2 enhances proliferation and inhibits apoptosis through activating Akt/mTORC1 signaling pathway in mouse preadipocytes.Journal of lipid research · 2015Article
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- Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well?Current diabetes reports · 2014Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe transcription factor, forkhead box (FOX)O1, is involved in fatty acid-induced apoptosis in pancreatic beta cells, but the precise mechanism is poorly understood. We aimed to identify which direct downstream targets of FOXO1 are involved in palmitate-induced apoptosis in the pancreatic beta cell line MIN6.
methodsChromatin immunoprecipitation (ChIP) coupled to a DNA selection and ligation technique (ChIP-DSL) was used to identify the direct targets of FOXO1. The mRNA level was examined by real-time PCR assay. The ChIP-DSL results were verified using ChIP-PCR and luciferase assay, respectively. The cell apoptosis rate was determined by TUNEL assay and by scoring cells with pycnotic nuclei.
resultsWe identified 189 target genes and selected 106 targets for expression analysis in MIN6 cells treated with palmitate. The results showed that six genes were significantly upregulated and four were downregulated. Binding of FOXO1 to the promoters was determined by ChIP-PCR and confirmed by luciferase assay. Among the ten up- and downregulated genes, mRNA expression of A930038C07Rik was significantly decreased and that of Ppa1 was increased in 8-week-old db/db mice. The apoptosis assay showed that overproduction of the protein 'RIKEN cDNA A930038C07' (A930038C07Rik) drastically enhanced palmitate-induced apoptosis, while pyrophosphatase (inorganic) 1 (PPA1) partially protected the cells from apoptosis. Knockdown of PPA1, moreover, significantly increased apoptosis. CONCLUSIONS/
interpretationWe identified for the first time FOXO1 targets in MIN6 cells treated with palmitate, thus revealing the important roles of A930038C07Rik and PPA1 in palmitate-induced cell apoptosis. These results shed light on the mechanisms of palmitate-induced apoptosis in pancreatic beta cells.
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