Effect of lysosomal storage on bis(monoacylglycero)phosphate
Effect of lysosomal storage on bis(monoacylglycero)phosphate
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DOI：
10.1042/bj20071043
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发表时间：
2008-04-01
影响因子：
4.1
通讯作者：
Fuller, Maria
中科院分区：
文献类型：
--
作者：
Meikle, Peter J.;Duplock, Stephen;Fuller, Maria
骨形态发生蛋白(BMP)是一种酸性磷脂，是PG(磷脂酰甘油)的结构异构体，由溶血磷脂酰甘油和甘油头基酯化的附加脂肪酸组成。它被认为是由PG在内体/溶酶体室合成的，主要存在于同一室内的多泡小体中。在本研究中，我们研究了溶酶体储存对8种不同LSD(溶酶体储存障碍)患者培养的成纤维细胞中BMP的影响以及20种LSD中的一种LSD患者的血浆样本。使用ESI-MS/MS(电喷雾电离串联MS)，我们能够证明在培养的成纤维细胞中BMP的个体种类的升高或改变，但PG的升高或改变。除Fabry病外，所有受影响的细胞系都显示出相对于单不饱和物种而言，多不饱和BMP物种的丢失，这与溶酶体功能障碍导致受影响细胞中的糖磷脂和胆固醇升高的文献报道相关，这些过程被认为是LSD发病的关键过程。涉及巨噬细胞储存和/或肝肿大的LSD患者的血浆样本显示，与对照血浆相比，C-18：1/C-18：1种BMP的血浆浓度升高，而主要涉及中枢神经系统病理的疾病患者的血浆BMP浓度没有升高。这些结果表明，BMP的释放是细胞/组织特异性的，它可能是LSD的一个子集的生物标志物。
BMP [bis(monoacylglycero)phosphate] is an acidic phospholipid and a structural isomer of PG (phosphatidylglycerol), consisting of lysophosphatidylglycerol with an additional fatty acid esterified to the glycerol head group. It is thought to be synthesized from PG in the endosomal/lysosomal compartment and is found primarily in multivesicular bodies within the same compartment. In the present study, we investigated the effect of lysosomal storage on BMP in cultured fibroblasts from patients with eight different LSDs (lysosomal storage disorders) and plasma samples from patients with one of 20 LSDs. Using ESI-MS/MS (electrospray ionization tandem MS), we were able to demonstrate either elevations or alterations in the individual species of BMP, but not of PG, in cultured fibroblasts. All affected cell lines, with the exception of Fabry disease, showed a loss of polyunsaturated BMP species relative to mono-unsaturated species, and this correlated with the literature reports of lysosomal dysfunction leading to elevations of glycosphingolipids and cholesterol in affected cells, processes thought to be critical to the pathogenesis of LSDs. Plasma samples from patients with LSDs involving storage in macrophages and/or with hepatomegaly showed an elevation in the plasma concentration of the C-18:1/C-18:1 species of BMP when compared with control plasmas, whereas disorders involving primarily the central nervous system pathology did not. These results suggest that the release of BMP is cell/tissue-specific and that it may be useful as a biomarker for a subset of LSDs.