Role of the AMP kinase in cytokine-induced human EndoC-βH1 cell death

被引：19

作者：

Fred, Rikard G. ^{[1
]}

Kappe, Camilla ^{[1
]}

Ameur, Adam ^{[2
]}

Cen, Jing ^{[1
]}

Bergsten, Peter ^{[1
]}

Ravassard, Phillippe ^{[3
]}

Scharfmann, Raphael ^{[4
]}

Welsh, Nils ^{[1
]}

机构：

[1] Uppsala Univ, Dept Med Cell Biol, Sci Life Lab, SE-75123 Uppsala, Sweden

[2] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, SE-75185 Uppsala, Sweden

[3] Univ Paris 06, Sorbonne Univ, Biotechnol & Biotherapy Lab,Inst Cerveau & Moelle, Inserm,U1127,CNRS UMR 7225,UMR S 1127,ICM,CHU Pit, Paris, France

[4] Univ Paris 05, Sorbonne Paris Cite, Fac Med, INSERM,U1016,Inst Cochin, F-75014 Paris, France

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2015年 / 414卷 / 0C期

关键词：

AMPK; ATP; EndoC-beta H1 cells; Cytokines; Apoptosis; NF-kappaB; STAT-1; ACTIVATED PROTEIN-KINASE; PANCREATIC BETA-CELLS; GAMMA ACTION; HUMAN ISLETS; APOPTOSIS; INHIBITION; TRANSCRIPTION; INTERLEUKIN-1; GLUCOSE; PHOSPHORYLATION;

D O I：

10.1016/j.mce.2015.07.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The aim of the present investigation was to delineate cytokine-induced signaling and death using the EndoC-beta H1 cells as a model for primary human beta-cells. The cytokines IL-1 beta and IFN-gamma induced a rapid and transient activation of NF-kappa B, STAT-1, ERK, JNK and eIF-2 alpha signaling. The EndoC-beta H1 cells died rapidly when exposed to IL-1 beta + IFN-gamma, and this occurred also in the presence of the actinomycin D. Inhibition of NF-kappa B and STAT-1 did not protect against cell death, nor did the cytokines activate iNOS expression. Instead, cytokines promoted a rapid decrease in EndoC-beta H1 cell respiration and ATP levels, and we observed protection by the AMPK activator AICAR against cytokine-induced cell death. It is concluded that EndoC-beta H1 cell death can be prevented by AMPK activation, which suggests a role for ATP depletion in cytokine-induced human beta-cell death. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：53 / 63

页数：11

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