Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2
Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2
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DOI：
10.1016/j.abb.2006.11.014
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发表时间：
2007-03-15
影响因子：
3.9
通讯作者：
Subbaiah, Papasani V.
中科院分区：
文献类型：
--
作者：
Singh, Dev K.;Gesquiere, Laurence R.;Subbaiah, Papasani V.
我们以前的研究表明，V型分泌型磷脂酶A（2）（sPLA（2）V）被鞘磷脂（SM）抑制，但被神经酰胺激活。在这里，我们研究了鞘脂结构对sPLA（2）V的活性和酰基特异性的影响。HDL SM降解为神经酰胺，但不降解为磷酸神经酰胺，刺激活性6倍，所有不饱和脂肪酸的释放受到同等影响。富含神经酰胺的HDL同样刺激了不饱和脂肪酸的释放。SM与磷脂酰胆碱（PC）脂质体的结合优先抑制16：0-20：4 PC的水解。相反，SMase C处理或神经酰胺掺入导致16：0-20：4 PC水解的优先刺激。神经酰胺中长链酰基的存在对于活化是必不可少的，长链二酰基甘油也是有效的。然而，磷酸神经酰胺具有抑制作用。这些研究表明，SM和神经酰胺在膜和脂蛋白不仅调节磷脂酶的活性，而且花生四烯酸，类花生酸的前体的释放。(c)2006年爱思唯尔公司All rights reserved.
We previously showed that group V secretory phospholipase A(2) (sPLA(2)V) is inhibited by sphingomyelin (SM), but activated by ceramide. Here, we investigated the effect of sphingolipid structure on the activity and acyl specificity of sPLA(2)V. Degradation of HDL SM to ceramide, but not to ceramide phosphate, stimulated the activity by 6-fold, with the release of all unsaturated fatty acids being affected equally. Ceramide-enrichment of HDL similarly stimulated the release of unsaturated fatty acids. Incorporation of SM into phosphatidylcholine (PC) liposomes preferentially inhibited the hydrolysis of 16:0-20:4 PC. Conversely, SMase C treatment or ceramide incorporation resulted in preferential stimulation of hydrolysis of 16:0-20:4 PC. The presence of a long chain acyl group in ceramide was essential for the activation, and long chain diacylglycerols were also effective. However, ceramide phosphate was inhibitory. These studies show that SM and ceramide in the membranes and lipoproteins not only regulate the activity of phospholipases, but also the release of arachidonate, the precursor of eicosanoids. (c) 2006 Elsevier Inc. All rights reserved.