The change of membrane fluidity in the model system of peroxisomal diseases

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 03670482
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: KAMOSITA Shigehiko University of Tokyo Sccomd Department of Intemal Medicine Professor, 医学部(病), 教授 (60048973)
• Co-Investigator(Kenkyū-buntansha): SAITO Makiko University of Tokyo Sccomd Department of Intemal Medicine Assistant Pro, 医学部(病), 助手 (20225733) ; SAKAKIHARA Yoichi University of Tokyo Sccomd Department of Intemal Medicine Lecturer, 医学部(病), 講師 (10143463)
• Project Period (FY): 1991 – 1993
• Keywords: C-6 glia / Thioridazine / Membrane fluidity / 2'3'cyclic nucleotide 3'phosphohydrase / lipid Composition

Research Abstract

In order to understand the relationship between peroxisomal dysfunction and clinical manifestations of peroxisomal disorders, the effect of tioridazine, a peroxisomal -oxidation antagonist, on C-6 glial cell differentiation, membrane lipid composition and membrane fluidity were examined. 2'3'cyclic nucleotide 3'phophohydrase (CNP) is considered to be a membrane associated enzyme closely related to myelination. In our study, induction of CNP was inhibited lignoceric acid (C24 : 0) to behenic acid (C22 : 0) in cell membrane lipids, which gave evidence that thioridazine caused impaired differenciation of glial stem cell system. Membrane fluidity of C-6 glial cells was exzamined using a fluorescent probe 1,6-diphenyl-1,3,5-hezatriene (DPH). DPH anisotropy value was decreased in the glial cells treated with thioridazine. From these results, it is implicated that the alteration of the membrane lipid composition caused by thioridazine would have3 some effect on the differentiation of glial cells via the changes in membrane properies.