Structures and biological activity of phosphorylated dihydroceramides of Porphyromonas gingivalis
Structures and biological activity of phosphorylated dihydroceramides of Porphyromonas gingivalis
复制标题
DOI：
10.1194/jlr.m400278-jlr200
复制
发表时间：
2004-12-01
影响因子：
6.5
通讯作者：
Smith, MB
中科院分区：
文献类型：
--
作者：
Nichols, FC;Riep, B;Smith, MB
牙龈卟啉单胞菌是一种公认的牙周病原体，它可以合成游离神经酰胺以及其他磷酸化的神经酰胺脂。本研究采用高效液相色谱（HPLC）法分离牙龈草的复合脂质，并测定其主要神经酰胺类的结构和生物活性。通过气相色谱-质谱、电喷雾串联质谱（ESI-MS/MS）和核磁共振分析，在特定的HPLC馏分中鉴定出三种主要的二氢神经酰胺，它们都含有相同的二氢神经酰胺碱基结构（3-OH isoC(17:0)，酰胺连接到17、18或19个碳的饱和长链碱基）。在HPLC馏分7 ~ 8中发现的游离二氢神经酰胺类生物活性较低。用1- o -磷酸甘油和与3-OH - isoC羟基（17:0）连接的isoC（15:0）取代的20种二氢神经酰胺，显著增强了白介素-1 β (il -1 β)介导的前列腺素分泌，并产生了成纤维细胞形态的显著改变。用1- o -磷酸乙醇胺取代的28个二氢神经酰胺的高效液相色谱（HPLC）分数显示，其增强il -1 - β介导的前列腺素分泌的能力很小。由牙龈卟啉卟啉合成的新型磷酸化二氢神经酰胺显示出不同的生物活性，基于磷酸化的头基取代和/或酯化脂肪酸的添加。这些结果还表明，牙龈P的磷酸甘油二氢神经酰胺具有很强的毒力，可以促进il -1 β处理的成纤维细胞分泌炎症因子，并在培养中产生明显的细胞形态改变。——尼科尔斯，E. C.， B. Riep， J. Mun， M. D. Morton， M. T. Bojarski， E. E. Dewhirst， M. B. Smith牙龈卟啉单胞菌磷酸化二氢神经酰胺的结构和生物活性。
Porphyromonas gingivalis, a recognized periodontal pathogen, synthesizes free ceramides as well as other phosphorylated ceramide lipids. The purpose of this study was to separate complex lipids of P gingivalis by high-performance liquid chromatography (HPLC) and determine the structures and biological activities of the major ceramide classes. Using gas chromatography-mass spectrometry, electrospray tandem mass spectrometry (ESI-MS/MS) and NMR analyses, three major classes of dihydroceramides were identified in specific HPLC fractions, with all classes containing the same dihydroceramide base structures (3-OH isoC(17:0) in amide linkage to saturated long-chain bases of 17, 18, or 19 carbons). The free dihydroceramide class recovered in HPLC fractions 7-8 revealed little biological activity. HPLC fraction 20 dihydroceramides, substituted with 1-O-phosphoglycerol and isoC(15:0) linked to the hydroxyl of 3-OH isoC(17:0), significantly potentiated interleukin-1beta (IL-1beta)-mediated prostaglandin secretion and produced marked alterations in fibroblast morphology. HPLC fraction 28 dihydroceramides, substituted with 1-O-phosphoethanolamine, demonstrated little capacity to potentiate IL-1beta-mediated prostaglandin secretion. The novel phosphorylated dihydroceramides synthesized by P. gingivalis demonstrate varying biological activities based on the phosphorylated head group substitution and/or the addition of esterified fatty acid. These results also demonstrate the strong virulence capacity of phosphoglycerol dihydroceramides of P gingivalis to promote inflammatory factor secretion from IL-1beta-treated fibroblasts and to produce marked alterations in cell morphology in culture.-Nichols, E C., B. Riep, J. Mun, M. D. Morton, M. T. Bojarski, E E. Dewhirst, and M. B. Smith. Structures and biological activity of phosphorylated dihydroceramides of Porphyromonas gingivalis.