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Abstract：
We studied the altered molecular species of lipids in brain and liver tissues, and fibroblasts from patients with Zellweger syndrome (ZS). ZS cerebellum samples contained a higher amount of sphingomyelin with shorter chain fatty acids compared to that in normal controls. The amount of phosphatidylethanolamine (PE) was less than half of that in controls, with the absence of the PE-type of plasmalogen. Gangliosides were accumulated in the brains and fibroblasts of ZS patients. To investigate whether or not impaired beta-oxidation of very long chain fatty acids and/or plasmalogen synthesis affects glycolipids metabolism, RNAi of peroxisomal acylCo-A oxidase (ACOX1) and glyceronephosphate O-acyltransferase (GNPAT) was performed using cultured neural cells. In neuronal F3-Ngn1 cells, ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucose ceramide glucosyltransferase (UGCG). These results suggest that both impaired beta-oxidation of very long chain fatty acids and plasmalogen synthesis affect glycolipid metabolism in neuronal cells.
摘要：
我们研究了大脑和肝脏组织中脂质分子种类的改变，和Zellweger综合征（ZS）患者的成纤维细胞。与正常对照相比，ZS小脑样品中的鞘磷脂含量较高，脂肪酸链较短。磷脂酰乙醇胺（PE）的含量不到对照组的一半，不存在PE型缩醛磷脂。神经节苷脂在ZS患者的脑和成纤维细胞中积累。为了研究极长链脂肪酸的β-氧化受损和/或缩醛磷脂合成是否会影响糖脂代谢，使用培养的神经细胞进行过氧化物酶体酰基Co-A氧化酶（ACOX1）和甘油磷酸O-酰基转移酶（GNPAT）的RNAi。在神经元F3-Ngn1细胞中，ACOX1和GNPAT沉默上调神经酰胺半乳糖基转移酶（UGT8）mRNA表达，下调UDP-葡萄糖神经酰胺葡萄糖基转移酶(UGCG)。这些结果表明，极长链脂肪酸的β-氧化受损和缩醛磷脂合成都会影响神经元细胞中的糖脂代谢。
