Effects of peroxisomal beta-oxidation antagonist on 2',3'-cyclic-nucleotide 3'-phosphohydrolase, membrane lipid compositions, and membrane fluidity in C-6 glial cells.
In order to understand the relationship between peroxisomal dysfunction and clinical manifestations of peroxisomal disorders, the effect of thioridazine, a peroxisomal beta-oxidation antagonist, on the differentiation, membrane lipid composition and membrane fluidity of C-6 glial cells was examined. In our study, induction of 2',3'-cyclic-nucleotide 3'-phosphohydrolase (CNP), which was considered to be a membrane-associated enzyme closely associated with myelination, was inhibited with supplementation of thioridazine, followed by an increase in the relative concentration of longer chain fatty acids in cell membrane lipids, indicating that thioridazine causes impaired differentiation in the glial stem cell system. Membrane fluidity of C-6 glial cells was examined using a fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). The DPH anisotropy value was decreased in the glial cells treated with thioridazine. These results indicate that the alteration of the membrane lipid composition caused by thioridazine affects the differentiation of glial cells via the changes in membrane properties.
Saito
M
M
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Japan.
Iimori
Y
Y
Kamoshita
S
S
Yanagisawa
M
M
Sakakihara
Y
Y
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002784:Cholesterol / Q000032:analysis; D004161:Diphenylhexatriene; D005227:Fatty Acids / Q000032:analysis; D005454:Fluorescence Polarization; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis*; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000032:analysis; D010727:Phosphoric Diester Hydrolases; D013881:Thioridazine / Q000494:pharmacology*
D005227:Fatty Acids; D008563:Membrane Lipids; D010743:Phospholipids; D004161:Diphenylhexatriene; D002784:Cholesterol; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D013881:Thioridazine