Pérez-Gordones Maria C, Lugo Miguel R, Winkler Moraima, Cervino Vincenza, Benaim Gustavo
Instituto de Biología Experimental (IBE), Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela.
Arch Biochem Biophys. 2009 Sep;489(1-2):55-61. doi: 10.1016/j.abb.2009.07.010. Epub 2009 Jul 23.
The plasma membrane Ca(2+)-ATPase (PMCA) plays a key role in the regulation of the intracellular Ca(2+) concentration. Ethanol stimulates this Ca(2+) pump in an isoform-specific manner. On search for a physiological molecule that could mimic the effect of ethanol, we have previously demonstrated that some sphingolipids containing free "hydroxyl" groups, like ceramide, are able to stimulate the PMCA. Since diacylglycerol (DAG) structurally shares some characteristics with ceramide, we evaluate its effect on the PMCA. We demonstrated that DAG is a potent stimulator of this enzyme. The activation induced is additive to that produced by calmodulin, protein-kinase C and ethanol, which implies that DAG interacts with the PMCA through a different mechanism. Additionally, by different fluorescent approaches, we demonstrated a direct binding between PMCA and DAG. The results obtained in this work strongly suggest that DAG is a novel effector of the PMCA, acting by a direct interaction.
质膜Ca(2+)-ATP酶（PMCA）在调节细胞内Ca(2+)浓度方面起着关键作用。乙醇以亚型特异性方式刺激这种Ca(2+)泵。在寻找一种能模拟乙醇作用的生理分子时，我们之前已经证明，一些含有游离“羟基”基团的鞘脂，如神经酰胺，能够刺激PMCA。由于二酰基甘油（DAG）在结构上与神经酰胺有一些共同特征，我们评估了其对PMCA的影响。我们证明DAG是这种酶的有效刺激剂。诱导的激活作用与钙调蛋白、蛋白激酶C和乙醇产生的激活作用相加，这意味着DAG通过不同机制与PMCA相互作用。此外，通过不同的荧光方法，我们证明了PMCA与DAG之间的直接结合。这项工作获得的结果有力地表明，DAG是PMCA的一种新型效应物，通过直接相互作用发挥作用。
