Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1038/cddis.2012.17
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Aflaki Elma
- Kratky Dagmar
- Co-Autor*innen der Med Uni Graz
- Doddapattar Prakash
- Graier Wolfgang
- Köfeler Harald
- Kolb Dagmar
- Malli Roland
- Radovic Branislav
- Rainer Silvia
- Vujic Nemanja
- Wegscheider Martin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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
- triacylglycerol
- C16 ceramide
- lipotoxicity
- macrophages
- apoptosis