Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Navigation/Suche
- Forscher*innen
- Institutionen
- Projekte
- Publikationen
- Partner
- Geldgeber
- Ausstattung
- Knowhow
- Forschungsfelder
"Köpfe" der aktuellen Meldungen:
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Vogl, F; Humpolickova, J; Amaro, M; Koller, D; Kofeler, H; Zenzmaier, E; Hof, M; Hermetter, A.
Role of protein kinase C delta in apoptotic signaling of oxidized phospholipids in RAW 264.7 macrophages
BBA-MOL CELL BIOL L. 2016; 1861(4): 320-330.
Doi: 10.1016/j.bbalip.2015.12.009
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Köfeler Harald
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The oxidized phospholipids (oxPl) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) are cytotoxic components of oxidized LDL (oxLDL). Sustained exposure to oxLDL or isolated oxPl induces apoptotic signaling in vascular cells, which is a hallmark of the late phase of atherosclerosis. Activation of sphingomyelinase, the coordinate formation of ceramide and activation of caspase 3/7 as well as the activation of stress-associated kinases are causally involved in this process. Here, we provide evidence for a role of PKCδ in oxPl cytotoxicity. Silencing of the enzyme by siRNA significantly reduced caspase 3/7 activation in RAW 264.7 macrophages under the influence of oxPl. Concomitantly, PKCδ was phosphorylated as a consequence of cell exposure to PGPC or POVPC. Single molecule fluorescence microscopy provided direct evidence for oxPl-protein interaction. Both oxPl recruited an RFP-tagged PKCδ to the plasma membrane in a concentration-dependent manner. In addition, two color cross-correlation number and brightness (ccN&B) analysis of the molecular motions revealed that fluorescently labeled PGPC or POVPC analogs co-diffuse and are associated with the fluorescent protein kinase in live cells. The underlying lipid-protein interactions may be due to chemical bonding (imine formation between the phospholipid aldehyde POVPC with protein amino groups) and physical association (with POVPC or PGPC). In summary, our data supports the assumption that PKCδ acts as a proapototic kinase in oxPl-included apoptosis of RAW 264.7 macrophages. The direct association of the bioactive lipids with this enzyme seems to be an important step in the early phase of apoptotic signaling. Copyright © 2015 Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - drug effects
- Caspase 3 - metabolism
- Caspase 7 - metabolism
- Dose-Response Relationship, Drug -
- Enzyme Activation -
- Gene Expression Regulation, Enzymologic -
- Genes, Reporter -
- Macrophages - drug effects
- Macrophages - enzymology
- Macrophages - pathology
- Mice -
- Oxidation-Reduction -
- Phospholipid Ethers - toxicity
- Phosphorylation -
- Protein Kinase C-delta - genetics
- Protein Kinase C-delta - metabolism
- RAW 264.7 Cells -
- RNA Interference -
- Signal Transduction - drug effects
- Time Factors -
- Transfection -
- Find related publications in this database (Keywords)
- Oxidized LDL
- Atherosclerosis
- Ceramide
- Acid sphingomyelinase
- Lipid-protein-interactions
- Fluorescent phospholipids