TY - JOUR T1 - Foodborne cereulide causes beta-cell dysfunction and apoptosis. JF - PLoS One Y1 - 2014 A1 - Vangoitsenhoven, Roman A1 - Rondas, Dieter A1 - Inne Crèvecoeur A1 - D'Hertog, Wannes A1 - Baatsen, Pieter A1 - Masini, Matilde A1 - Mirjana Andjelkovic A1 - Joris Van Loco A1 - Matthys, Christophe A1 - Mathieu, Chantal A1 - Overbergh, Lut A1 - Van der Schueren, Bart KW - Animals KW - Apoptosis KW - Cell Line KW - Cercopithecus aethiops KW - COS Cells KW - Depsipeptides KW - Food Microbiology KW - Glucose KW - Hep G2 Cells KW - Humans KW - Insulin KW - Insulin-Secreting Cells KW - Islets of Langerhans KW - mice KW - Mice, Inbred C57BL KW - Mitochondria KW - rats AB -

AIMS/HYPOTHESIS: To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function.

METHODS: Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6) and rat (INS-1E) beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1). Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS). Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.

RESULTS: 24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05). Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05) and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein). Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05) and reactive oxygen species increased by more than twofold (P<0.05) following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.

CONCLUSIONS/INTERPRETATION: Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.

VL - 9 CP - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25119564?dopt=Abstract M3 - 10.1371/journal.pone.0104866 ER -