Role of protein kinase C δ in apoptotic signaling of oxidized phospholipids in RAW 264.7 macrophages
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F16%3A00456379" target="_blank" >RIV/61388955:_____/16:00456379 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bbalip.2015.12.009" target="_blank" >http://dx.doi.org/10.1016/j.bbalip.2015.12.009</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbalip.2015.12.009" target="_blank" >10.1016/j.bbalip.2015.12.009</a>
Alternative languages
Result language
angličtina
Original language name
Role of protein kinase C δ in apoptotic signaling of oxidized phospholipids in RAW 264.7 macrophages
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CF - Physical chemistry and theoretical chemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GC14-03141J" target="_blank" >GC14-03141J: Exploring the structure function relationship of membrane-pore-forming FGF2 oligomers - a single molecule approach</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids
ISSN
1388-1981
e-ISSN
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Volume of the periodical
1861
Issue of the periodical within the volume
4
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
320-330
UT code for WoS article
000371940300006
EID of the result in the Scopus database
2-s2.0-84955559985