Altered phospholipid molecular species and glycolipid composition in brain, liver and fibroblasts of Zellweger syndrome.
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.
Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Japan.
Celine
C
Miyazaki
Makiko
M
Saitoh
Masayuki
M
Itoh
Sumimasa
S
Yamashita
Makoto
M
Miyagishi
Sachio
S
Takashima
Ann B
AB
Moser
Masao
M
Iwamori
Masashi
M
Mizuguchi
D042962:Acyl-CoA Oxidase; D000217:Acyltransferases / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020868:Gene Silencing; D005964:Glucosyltransferases / Q000096:biosynthesis; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism*; D008297:Male; D051146:N-Acylsphingosine Galactosyltransferase / Q000096:biosynthesis; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D015211:Zellweger Syndrome / Q000378:metabolism*
D006017:Glycolipids; D010743:Phospholipids; D010088:Oxidoreductases; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase; D005964:Glucosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase; C023246:ceramide glucosyltransferase
ACOX1; CDH; CMH; CNS; CTH; DBP; G6PDH; GNPAT; Ganglioside; PBS; PC; PE; Peroxisome; Plasmalogen; RNAi; Sphingomyelin; UGCG; UGT8; VLCFA; ZS; Zellweger syndrome; central nervous system; ceramide dihexoside; ceramide galactosyltransferase; ceramide glucosyltransferase; ceramide monohexoside; ceramide trihexoside; d-bifunctional protein; glucose-6-phosphate dehydrogenase; glyceronephosphate O-acyltransferase; peroxisomal acyl coenzyme-A oxidase; phosphate-buffered saline; phosphatidylcholine; phosphatidylethanolamine; very long chain fatty acid