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

Author:
Fred, Rikard G., Kappe, Camilla, Ameur, Adam, Cen, Jing, Bergsten, Peter, Ravassard, Phillippe, Scharfmann, Raphael, Welsh, Nils
Source:
Molecular and Cellular Endocrinology 2015 v.414 pp. 53-63
ISSN:
0303-7207
Subject:
AMP-activated protein kinase, adenosine triphosphate, cell death, cell respiration, humans, inducible nitric oxide synthase, interferon-gamma, interleukin-1beta, islets of Langerhans, mitogen-activated protein kinase, models, transcription factor NF-kappa B
Abstract:
The aim of the present investigation was to delineate cytokine-induced signaling and death using the EndoC-βH1 cells as a model for primary human beta-cells. The cytokines IL-1β and IFN-γ induced a rapid and transient activation of NF-κB, STAT-1, ERK, JNK and eIF-2α signaling. The EndoC-βH1 cells died rapidly when exposed to IL-1β + IFN-γ, and this occurred also in the presence of the actinomycin D. Inhibition of NF-κB and STAT-1 did not protect against cell death, nor did the cytokines activate iNOS expression. Instead, cytokines promoted a rapid decrease in EndoC-βH1 cell respiration and ATP levels, and we observed protection by the AMPK activator AICAR against cytokine-induced cell death. It is concluded that EndoC-βH1 cell death can be prevented by AMPK activation, which suggests a role for ATP depletion in cytokine-induced human beta-cell death.
Agid:
5523027