Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency
Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency
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DOI：
10.1016/j.bbalip.2014.01.001
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Fujiki, Yukio
中科院分区：
文献类型：
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作者：
Abe, Yuichi;Honsho, Masanori;Fujiki, Yukio
过氧体是一种亚细胞器，参与多种合成代谢和分解代谢过程，包括超长链脂肪酸的β-氧化和乙醚磷脂的生物合成。由过氧化体生物发生缺陷或过氧化体β-氧化引起的过氧酶体紊乱表现为严重的中枢神经系统紊乱。过氧化体代谢异常被认为是导致这些疾病的临床症状的原因，但其分子发病机制仍有待阐明。我们通过脂组学分析鉴定了Zellweger综合征(ZS)、酰基辅酶A氧化酶1(AOX)缺乏症、D-双功能蛋白(D-BP)和X-连锁肾上腺脑白质营养不良(X-ALD)患者成纤维细胞中的异常代谢产物，以及过氧酶体缺陷的中国仓鼠卵巢细胞突变体。在过氧化体生物合成缺乏的细胞中，血浆乙醇胺显著减少，磷脂酰乙醇胺增加。在所有突变细胞中都观察到磷脂酰胆碱中极长链饱和脂肪酸和单不饱和脂肪酸的显著积累。极长链多不饱和脂肪酸(VLC-PUFA)水平显著升高，而含有二十二碳六烯酸(DHA)的磷脂(DHA，C22：6N-3)在ZS、AOX缺乏症和D-BP缺乏症患者的成纤维细胞中减少，但在X-ALD患者的成纤维细胞中没有。由于AOX缺乏症患者的症状比X-ALD患者更严重，VLC-PUFA的积聚和/或DHA的减少可能与过氧化体疾病的严重程度有关。(C)2014爱思唯尔B.V.保留所有权利。
Peroxisomes are subcellular organelles that function in multiple anabolic and catabolic processes, including beta-oxidation of very-long-chain fatty acids (VLCFA) and biosynthesis of ether phospholipids. Peroxisomal disorders caused by defects in peroxisome biogenesis or peroxisomal beta-oxidation manifest as severe neural disorders of the central nervous system. Abnormal peroxisomal metabolism is thought to be responsible for the clinical symptoms of these diseases, but their molecular pathogenesis remains to be elucidated. We performed lipidomic analysis to identify aberrant metabolites in fibroblasts from patients with Zellweger syndrome (ZS), acyl-CoA oxidase1 (AOx) deficiency, D-bifunctional protein (D-BP) and X-linked adrenoleukodystrophy (X-ALD), as well as in peroxisome-deficient Chinese hamster ovary cell mutants. In cells deficient in peroxisomal biogenesis, plasmenylethanolamine was remarkably reduced and phosphatidylethanolamine was increased. Marked accumulation of very-long-chain saturated fatty acid and monounsaturated fatty acids in phosphatidylcholine was observed in all mutant cells. Very-long-chain polyunsaturated fatty acid (VLC-PUFA) levels were significantly elevated, whilst phospholipids containing docosahexaenoic acid (DHA, C22:6n-3) were reduced in fibroblasts from patients with ZS, AOx deficiency, and D-BP deficiency, but not in fibroblasts from an X-ALD patient. Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases. (C) 2014 Elsevier B.V. All rights reserved.