Protein kinase C-beta and -delta isoenzymes promote arachidonic acid production and proliferation of MonoMac-6 cells.
In this study, we investigated the putative roles of certain protein kinase C (PKC) isoenzymes in the regulation of proliferation and arachidonic acid (AA) release in the human monocytoid MonoMac-6 cell line. Experiments employing specific PKC inhibitors and molecular biological methods (RNA-interference, recombinant overexpression) revealed that the two dominantly expressed isozymes, i.e., the "conventional" cPKCbeta and the "novel" nPKCdelta, promote AA production and cellular proliferation. In addition, using different phospholipase A(2) (PLA(2)) inhibitors, we were able to show that the calcium-independent iPLA(2) as well as diacylglycerol lipase (but not the cytosolic PLA(2)) function as "downstream" targets of cPKCbeta and nPKCdelta. In addition, we have also found that, among the other existing PKC isoforms, cPKCalpha plays a minor inhibitory role, whereas nPKCvarepsilon and aPKCzeta apparently do not regulate these cellular processes. In conclusion, in this paper we provide the first evidence that certain PKC isoforms play pivotal, specific, and (at least partly) antagonistic roles in the regulation of AA production and cellular proliferation of human monocytoid MonoMac-6 cells.
Griger
Zoltán
Z
Department of Physiology, University of Debrecen, Research Center for Molecular Medicine, Medical and Health Science Center, Nagyerdei krt. 98., 4032, Debrecen, Hungary.
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Kovács
Ildikó
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Tóth
Balázs I
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Kovács
László
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Sipka
Sándor
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Bíró
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D016718:Arachidonic Acid / Q000096:biosynthesis*; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D034741:RNA, Small Interfering; C081021:Go 6976; D049452:Green Fluorescent Proteins; D016718:Arachidonic Acid; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate