Molecular Species of Phospholipids with Very Long Chain Fatty Acids in Skin Fibroblasts of Zellweger Syndrome
Molecular Species of Phospholipids with Very Long Chain Fatty Acids in Skin Fibroblasts of Zellweger Syndrome
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DOI：
10.1007/s11745-013-3848-5
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发表时间：
2013-12-01
期刊：
影响因子：
1.9
通讯作者：
Yokoyama, Kazuaki
中科院分区：
文献类型：
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作者：
Hama, Kotaro;Nagai, Toru;Yokoyama, Kazuaki
患者脂质中C-26：0/C-22：0脂肪酸的比率被广泛接受为过氧化物酶体疾病（例如Zellweger综合征和X连锁肾上腺脑白质营养不良（X-ALD））的关键临床标准。然而，具有极长链脂肪酸（VLCFA）的磷脂分子种类尚未被精确表征。在本研究中，这些分子的结构在成纤维细胞的Zellweger综合征和X-ALD检查使用LC-ESI-MS/MS分析。在Zellweger患者的成纤维细胞中，在几种磷脂类以及中性脂质（包括三酰甘油和胆固醇酯）中检测到大量含VLCFA的分子种类。在这些脂质中，磷脂酰胆碱表现出最多样性的VLCFA分子物种的结构。一些VLCFA具有比C-26：0-脂肪酸（FA）更长的碳链和/或更多的双键。在其他磷脂类中也发现了类似的VLCFA，如磷脂酰乙醇胺和磷脂酰丝氨酸。此外，含有VLCFA的磷脂物质在来自Zellweger患者的成纤维细胞中显示出一些差异。似乎具有VLCFA的磷脂，具有或不具有双键，以及C-26：0-FA可能影响细胞功能，从而导致过氧化物酶体疾病的发病机制，例如Zellweger综合征和X-ALD。
The ratio of C-26:0/C-22:0 fatty acids in patient lipids is widely accepted as a critical clinical criterion of peroxisomal diseases, such as Zellweger syndrome and X-linked adrenoleukodystrophy (X-ALD). However, phospholipid molecular species with very long chain fatty acids (VLCFA) have not been precisely characterized. In the present study, the structures of such molecules in fibroblasts of Zellweger syndrome and X-ALD were examined using LC-ESI-MS/MS analysis. In fibroblasts from Zellweger patients, a large number of VLCFA-containing molecular species were detected in several phospholipid classes as well as neutral lipids, including triacylglycerol and cholesteryl esters. Among these lipids, phosphatidylcholine showed the most diversity in the structures of VLCFA-containing molecular species. Some VLCFA possessed longer carbon chains and/or larger number of double bonds than C-26:0-fatty acid (FA). Similar VLCFA were also found in other phospholipid classes, such as phosphatidylethanolamine and phosphatidylserine. In addition, VLCFA-containing phospholipid species showed some differences among fibroblasts from Zellweger patients. It appears that phospholipids with VLCFA, with or without double bonds, as well as C-26:0-FA might affect cellular functions, thus leading to the pathogenesis of peroxisomal diseases, such as Zellweger syndrome and X-ALD.