Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Japan.
Neurosci Lett. 2013 Sep 27;552:71-5. doi: 10.1016/j.neulet.2013.07.045. Epub 2013 Aug 7.
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.
我们研究了 Zellweger 综合征（ZS）患者的脑组织、肝组织和成纤维细胞中脂质的分子种类变化。与正常对照组相比，ZS 小脑组织中的神经鞘磷脂含有更多短链脂肪酸。磷脂酰乙醇胺（PE）的含量不到对照组的一半，而且缺乏 PE 型血浆类脂。神经节苷脂在 ZS 患者的大脑和成纤维细胞中积累。为了研究是否由于极长链脂肪酸β氧化缺陷和/或血浆类脂合成障碍影响糖脂代谢，我们使用培养的神经细胞进行过氧化物酶体酰基辅酶 A 氧化酶（ACOX1）和甘油磷酸 O-酰基转移酶（GNPAT）的 RNAi 实验。在神经元 F3-Ngn1 细胞中，ACOX1 和 GNPAT 的沉默上调了半乳糖脑苷脂转移酶（UGT8）mRNA 的表达，下调了 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β氧化缺陷和血浆类脂合成障碍均影响神经元细胞中的糖脂代谢。
