Genome-wide identification of palmitate-regulated immediate early genes and target genes in pancreatic beta-cells reveals a central role of NF-κB = 췌장 베타세포에서 palmitate에 의해 조절되는 immediate early gene과 타겟유전자 동정을 통한 NF-κB의 역할

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Title
Genome-wide identification of palmitate-regulated immediate early genes and target genes in pancreatic beta-cells reveals a central role of NF-κB = 췌장 베타세포에서 palmitate에 의해 조절되는 immediate early gene과 타겟유전자 동정을 통한 NF-κB의 역할
Author(s)
H J Choi; Seungwoo Hwang; S H Lee; Y R Lee; J Shin; K S Park; Y M Cho
Bibliographic Citation
Molecular Biology Reports, vol. 39, no. 6, pp. 6781-6789
Publication Year
2012
Abstract
Free fatty acid-induced pancreatic β-cell dysfunction plays a key role in the pathogenesis of type 2 diabetes. We conducted gene expression microarray analysis to comprehensively investigate the transcription machinery of palmitate-regulated genes in pancreatic β-cells in vitro. In particular, mouse pancreatic βTC3 cells were treated with palmitate in the presence or absence of cycloheximide (CHX), which blocks protein synthesis and thereby allows us to distinguish immediate early genes (IEGs) from their target genes. The microarray experiments identified 34 palmitate-regulated IEGs and 74 palmitate-regulated target genes. In silico promoter analysis revealed that transcription factor binding sites for NF-κB were over-represented, regulating approximately one-third of the palmitate-regulated target genes. In cells treated with CHX, nfkb1 showed an up-reg-ulation bypalmitate, suggesting that NF-κB couldbean IEG. Functional enrichment analysis of 27 palmitate-regulated genes with NF-κB binding sites showed an over-representation of genes involved in immune response, inflammatory response, defense response, taxis, regulation of cell proliferation, and regulation of cell death pathways. Elec-trophoretic mobility shift assay showed that palmitate stimulates NF-KB activity both in the presence and absence of CHX. In conclusion, by identifying IEGs and target genes, the present study depicted a comprehensive view of transcription machinery underlying palmitate-induced inflammation and cell proliferation/death in pancreatic β-cells and our data demonstrated the central role of NF-KB.
Keyword
Fatty acids, NonesterifiedGenes, Immediate-earlyInsulin-secreting cellsNF-kappa BOligonucleotide array sequence analysisPalmitates
ISSN
0301-4851
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s11033-012-1503-5
Type
Article
Appears in Collections:
Korea Bioinformation Center > 1. Journal Articles
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