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The linoleic acid derivative DCP-LA selectively activates PKC-epsilon, possibly binding to the phosphatidylserine binding site.
- Source :
-
Journal of lipid research [J Lipid Res] 2006 Jun; Vol. 47 (6), pp. 1146-56. Date of Electronic Publication: 2006 Mar 06. - Publication Year :
- 2006
-
Abstract
- This study examined the effect of 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on protein kinase C (PKC) activity. In the in situ PKC assay with reverse-phase high-performance liquid chromatography, DCP-LA significantly activated PKC in PC-12 cells in a concentration-dependent (10 nM-100 microM) manner, with the maximal effect at 100 nM, and the DCP-LA effect was blocked by GF109203X, a PKC inhibitor, or a selective inhibitor peptide of the novel PKC isozyme PKC-epsilon. Furthermore, DCP-LA activated PKC in HEK-293 cells that was inhibited by the small, interfering RNA against PKC-epsilon. In the cell-free PKC assay, of the nine isozymes examined here, DCP-LA most strongly activated PKC-epsilon, with >7-fold potency over other PKC isozymes, in the absence of dioleoyl-phosphatidylserine and 1,2-dioleoyl-sn-glycerol; instead, the DCP-LA action was inhibited by dioleoyl-phosphatidylserine. DCP-LA also activated PKC-gamma, a conventional PKC, but to a much lesser extent compared with that for PKC-epsilon, by a mechanism distinct from PKC-epsilon activation. Thus, DCP-LA serves as a selective activator of PKC-epsilon, possibly by binding to the phosphatidylserine binding site on PKC-epsilon. These results may provide fresh insight into lipid signaling in PKC activation.
- Subjects :
- Animals
Base Sequence
Binding Sites
Caprylates metabolism
Cell Line
Enzyme Activation drug effects
Enzyme Inhibitors pharmacology
Humans
Isoenzymes antagonists & inhibitors
Isoenzymes genetics
Isoenzymes metabolism
Linoleic Acids chemistry
Linoleic Acids metabolism
Linoleic Acids pharmacology
PC12 Cells
Phosphatidylserines chemistry
Phosphatidylserines pharmacology
Protein Kinase C antagonists & inhibitors
Protein Kinase C genetics
Protein Kinase C metabolism
Protein Kinase C-epsilon antagonists & inhibitors
Protein Kinase C-epsilon genetics
RNA, Small Interfering genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Substrate Specificity
Caprylates pharmacology
Phosphatidylserines metabolism
Protein Kinase C-epsilon metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2275
- Volume :
- 47
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 16520488
- Full Text :
- https://doi.org/10.1194/jlr.M500329-JLR200