Effect of TNF-α on the expression of ABCA1 in pancreatic β-cells

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28576
Title
Effect of TNF-α on the expression of ABCA1 in pancreatic β-cells
File
Description

Abstract

ATP-binding cassette transporter A1 (ABCA1), a 254-kD membrane protein, is a key regulator of lipid efflux from cells to apolipoproteins. ABCA1 in pancreatic β-cells influences insulin secretion and cholesterol homeostasis. Tumor necrosis factor (TNF)-α is a pleiotropic cytokine that elicits a wide spectrum of physiological events, including cell proliferation, differentiation, and apoptosis, and is also known to decrease glucose-dependent insulin secretion in pancreatic islets. In the present study, we examined the role of TNF-α on ABCA1 expression in rat pancreatic islets and INS-1 cells. ABCA1 protein levels decreased in response to rising concentrations of TNF-α in pancreatic islets. Real-time polymerase chain reaction analysis showed a significant decrease in ABCA1 mRNA expression. In parallel with its effect on endogenous ABCA1 mRNA levels, TNF-α suppressed the activity of a reporter construct containing the ABCA1 promoter. This effect was abrogated by BIRB796, but not by SB203580 or PD98095. The constitutively active form of p38 mitogen-activated protein kinase (MAPK) γ suppressed ABCA1 promoter activity but not p38-MAPK (α, β), while a dominant-negative mutant of p38-MAPK γ blocked the effect of TNF-α on ABCA1 promoter activity. BIRB796 inhibited the increased cholesterol ester content induced by TNF-α. However, BIRB796 had no effect on the decreased insulin content nor ABCA1 suppression caused by TNF-α in INS-1 cells. In summary, TNF-α suppressed the expression of endogenous ABCA1 in pancreatic islets and INS-1 cells. These findings raise the possibility that TNF-α may affect insulin secretion by controlling ABCA1 expression.

(医博甲700)

Author
著者 佐藤 誠祐
著者(ヨミ) サトウ セイスケ
著者(別表記) Sato Seisuke
Publication Title
Journal of Molecular Endocrinology
Publication Title Alternative
J Mol Endocrinol.
Volume
61
Issue
4
Start Page
185
End Page
193
Publisher
BioScientifica
Society for Endocrinology
Published Date
2018-10-15
ISSN
0952-5041
NCID
AA10675676
PMID
30131353
DOI
10.1530/JME-18-0167
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1530/JME-18-0167
出版社版Abstract : https://jme.bioscientifica.com/abstract/journals/jme/61/4/JME-18-0167.xml
ResearchGate: https://www.researchgate.net/publication/327144915_Effect_of_TNF-a_on_the_expression_of_ABCA1_in_pancreatic_b-cells
Rights
Copyright: © 2018 Society for Endocrinology 2018
Copyright © 2019 Bioscientifica Ltd
"This is the Accepted Version of the following article: Effect of TNF-α on the expression of ABCA1 in pancreatic β-cells; Journal of Molecular Endocrinology; Volume 61 Issue 4 (2018) Pages: 185-193; doi: 10.1530/JME-18-0167 , which has been published in final form at https://doi.org/10.1530/JME-18-0167 . "
エンバーゴ期間満了 / The embargo period has expired.
Text Version
ETD
Grant ID
博甲第700号
Grant Date
2018-12-26
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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