Implication of acyl chain of diacylglycerols in activation of different isoforms of protein kinase C.
We synthesized diacylglycerols (DAGs) containing omega-6 or omega-3 polyunsaturated fatty acids [i.e., 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDG), and 1-stearoyl-2-eicosapentaenoyl-sn-glycerol (SEG)] and assessed their efficiency on activation of conventional (alpha, beta I, gamma) and novel (epsilon, delta) protein kinase C (PKC). SAG exerted significantly higher stimulatory effects than SDG and SEG on activation of PKC alpha and PKC delta. Activation of PKC beta I by SEG and SDG was higher than that by SAG. Activation of PKC gamma did not differ significantly among DAG molecular species. Addition of SAG to assays containing SEG and SDG exerted additive effects on activation of alpha and epsilon, but not on beta I and gamma, isoforms of PKC. SDG- and SEG-induced activation of PKC delta was significantly curtailed by the addition of SAG. Three DAG species significantly curtailed the PMA-induced activation of beta Iota, gamma, and delta, but not of alpha and epsilon, isoforms of PKC. Our study demonstrates for the first time that in vitro activation of different PKC isoenzymes vary in response to different DAG species, and one can envisage that this differential regulation may be responsible for their in vivo effects on target organs.
Madani
S
S
Université de Bourgogne, UPRES Lipides et Nutrition EA 2422, Faculté des Sciences, F-21000 Dijon, France.
Hichami
A
A
Legrand
A
A
Belleville
J
J
Khan
N A
NA
D004075:Diglycerides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007527:Isoenzymes; D010718:Phosphatidylserines; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate