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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenylate Kinase / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cell Respiration / drug effects
  • Dactinomycin / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / enzymology
  • Interferon-gamma / pharmacology*
  • Interleukin-1beta / pharmacology*
  • Mice
  • Peptide Fragments / pharmacology*
  • Ribonucleotides / pharmacology
  • Signal Transduction / drug effects

Substances

  • Interleukin-1beta
  • Peptide Fragments
  • Ribonucleotides
  • interleukin-1beta (163-171)
  • Dactinomycin
  • Aminoimidazole Carboxamide
  • Interferon-gamma
  • Adenosine Triphosphate
  • Adenylate Kinase
  • AICA ribonucleotide