title: Role of the AMP kinase in cytokine-induced human EndoC-βH1 cell death.
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.
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
authors.forename: Rikard G
authors.initials: RG
authors.lastname: Fred
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Kappe
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
authors.forename: Jing
authors.initials: J
authors.lastname: Cen
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergsten
authors.affiliation: 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.
authors.forename: Phillippe
authors.initials: P
authors.lastname: Ravassard
authors.affiliation: INSERM, U1016, Institut Cochin, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Scharfmann
authors.affiliation: 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.
authors.forename: Nils
authors.initials: N
authors.lastname: Welsh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D010446:Peptide Fragments; D012265:Ribonucleotides; C052994:interleukin-1beta (163-171); D003609:Dactinomycin; D000620:Aminoimidazole Carboxamide; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; C031143:AICA ribonucleotide
keywords: AMPK; ATP; Apoptosis; Cytokines; EndoC-βH1 cells; NF-kappaB; STAT-1