Griger Zoltán, Páyer Edit, Kovács Ildikó, Tóth Balázs I, Kovács László, Sipka Sándor, Bíró Tamás
Department of Physiology, University of Debrecen, Research Center for Molecular Medicine, Medical and Health Science Center, Nagyerdei krt. 98., 4032, Debrecen, Hungary.
J Mol Med (Berl). 2007 Sep;85(9):1031-42. doi: 10.1007/s00109-007-0209-y. Epub 2007 Jun 5.
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.
在本研究中，我们调查了某些蛋白激酶C（PKC）同工酶在人单核细胞样MonoMac-6细胞系增殖调控和花生四烯酸（AA）释放中的假定作用。采用特异性PKC抑制剂和分子生物学方法（RNA干扰、重组过表达）的实验表明，两种主要表达的同工酶，即“传统”的cPKCβ和“新型”的nPKCδ，促进AA产生和细胞增殖。此外，使用不同的磷脂酶A2（PLA2）抑制剂，我们能够证明钙非依赖性iPLA2以及二酰甘油脂肪酶（而非胞质PLA2）作为cPKCβ和nPKCδ的“下游”靶点发挥作用。此外，我们还发现，在其他现有的PKC同工型中，cPKCα发挥次要的抑制作用，而nPKCε和aPKCζ显然不调节这些细胞过程。总之，在本文中我们首次提供证据表明，某些PKC同工型在人单核细胞样MonoMac-6细胞的AA产生和细胞增殖调控中发挥关键、特定且（至少部分）拮抗的作用。
