Investigation of pathogenesis of CNS lesions in patients with peroxisome biogenesis disorders

点击翻译按钮获取中文摘要

The study was conducted to determine the changes in the compositions and metabolism of lipids in peroxisome biogenesis disorders. In the cerebral cortex of a ZS patient, the amounts of ceramide monohexoside (CMH) and cholesterol ester (CE) increased in comparison to control levels of various ages. Although CMH accumulated with age in the white matter, absence of increase of CMH was recognized in ZS. Analysis of molecular species of PC plus PS fraction revealed significant increase of dipalmytoyl glycerophospholipids in cerebral cortex of ZS. We also analyzed lipids composition in ZP102 cells defect peroxisomes and exhibit impairments of peroxisomal β-oxidation of fatty acids and biosynthesis of plasmalogen. The concentration of free fatty acids in ZP102 cells was twice that in CHO-K1 cells, but their methyl esters and triacylglycerol in ZP102 cells were decreased in comparison to the control cells. Also, the concentration of CMH in ZP102 cells was significantly increased compared to that in the control cells, and the fatty acid molecular species, particularly the ratio of saturated and unsaturated ones, of individual lipids were different between two cell types. The rate of incorporation of [^<14>C] labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was higher than that in CHO-K1 cells. Lignoceric acid incorporated into cells was dominantly utilized for the synthesis of SM at 24 hr after removal of [^<14>C] lignoceric acid from the culture medium. ZP102 cells showed lower membrane mobility as compared to CHO-K1 cells. Alteration of lipid metabolism in particular enhanced metabolism of saturated fatty acids and sphingolipids may be related to the reduced membrane fluidity of ZP102 cells, which is implicated in dysfunction of membrane-linked processes in PBD