Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Aflaki, E; Doddapattar, P; Radovic, B; Povoden, S; Kolb, D; Vujic, N; Wegscheider, M; Koefeler, H; Hornemann, T; Graier, WF; Malli, R; Madeo, F; Kratky, D.
C16 ceramide is crucial for triacylglycerol-induced apoptosis in macrophages.
Cell Death Dis. 2012; 3(6):e280-e280 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Aflaki Elma
Doddapattar Prakash
Graier Wolfgang
Köfeler Harald
Kolb-Lenz Dagmar
Kratky Dagmar
Malli Roland
Radovic Branislav
Rainer Silvia
Vujic Nemanja
Wegscheider Martin

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
| | | | | | |
Triacylglycerol (TG) accumulation caused by adipose triglyceride lipase (ATGL) deficiency or very low-density lipoprotein (VLDL) loading of wild-type (Wt) macrophages results in mitochondrial-mediated apoptosis. This phenotype is correlated to depletion of Ca(2+) from the endoplasmic reticulum (ER), an event known to induce the unfolded protein response (UPR). Here, we show that ER stress in TG-rich macrophages activates the UPR, resulting in increased abundance of the chaperone GRP78/BiP, the induction of pancreatic ER kinase-like ER kinase, phosphorylation and activation of eukaryotic translation initiation factor 2A, the translocation of activating transcription factor (ATF)4 and ATF6 to the nucleus and the induction of the cell death executor CCAAT/enhancer-binding protein homologous protein. C16:0 ceramide concentrations were increased in Atgl-/- and VLDL-loaded Wt macrophages. Overexpression of ceramide synthases was sufficient to induce mitochondrial apoptosis in Wt macrophages. In accordance, inhibition of ceramide synthases in Atgl-/- macrophages by fumonisin B1 (FB1) resulted in specific inhibition of C16:0 ceramide, whereas intracellular TG concentrations remained high. Although the UPR was still activated in Atgl-/- macrophages, FB1 treatment rescued Atgl-/- macrophages from mitochondrial dysfunction and programmed cell death. We conclude that C16:0 ceramide elicits apoptosis in Atgl-/- macrophages by activation of the mitochondrial apoptosis pathway.
Find related publications in this database (using NLM MeSH Indexing)
Activating Transcription Factor 4 - metabolism
Activating Transcription Factor 6 - metabolism
Animals -
Apoptosis - drug effects
CCAAT-Enhancer-Binding Proteins - metabolism
Calcium - deficiency
Ceramides - metabolism
Endoplasmic Reticulum - drug effects
Enzyme Inhibitors - pharmacology
Fumonisins - pharmacology
Heat-Shock Proteins - metabolism
Humans -
Lipase - antagonists & inhibitors
Lipoproteins, VLDL - metabolism
Macrophages - cytology
Male -
Mice -
Mice, Knockout -
Mitochondria - drug effects
Signal Transduction - drug effects
Triglycerides - metabolism
Unfolded Protein Response - drug effects

Find related publications in this database (Keywords)
adipose triglyceride lipase deficiency
C16 ceramide
© Meduni Graz Impressum