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Mol Cell Endocrinol. 2015 Oct 15;414:53-63. doi: 10.1016/j.mce.2015.07.015. Epub 2015 Jul 26.

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

Author information

1
Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
2
Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
3
Biotechnology and Biotherapy Laboratory, Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, CHU Pitié-Salpêtrière, Paris, France.
4
INSERM, U1016, Institut Cochin, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France.
5
Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden. Electronic address: nils.welsh@mcb.uu.se.

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.

KEYWORDS:

AMPK; ATP; Apoptosis; Cytokines; EndoC-βH1 cells; NF-kappaB; STAT-1

PMID:
26213325
DOI:
10.1016/j.mce.2015.07.015
[Indexed for MEDLINE]

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