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

过氧化物酶体生物合成障碍患者中枢神经系统病变发病机制的研究

• 批准号: 15591086
• 负责人: SAKAKIHARA Yoichi
• 金额: $ 2.11万
• 依托单位: Ochanomizu University (2004-2005)The University of Tokyo (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591086/
• 关键词: Zellweger sundrome; peroxisome; ceramide monohexoside; membrane fluifdity; Z65細胞; プラズマローゲン; 過酸化水素; コレステロールエステル; セレブロシド; ホスファチジルコリン; Pex5; ZP102細胞

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

本研究旨在确定过氧化物酶体生物发生障碍中脂质组成和代谢的变化。在ZS患者的大脑皮层中，神经酰胺单己糖（CMH）和胆固醇酯（CE）的数量与不同年龄的对照水平相比有所增加。虽然CMH在白质中随着年龄的增长而积累，但在ZS中没有发现CMH的增加。PC加PS组分的分子种类分析显示，ZS大脑皮层双棕榈酰甘油磷脂显著增加。我们还分析了ZP102细胞缺陷过氧化物酶体的脂质组成，并发现过氧化物酶体β-脂肪酸氧化和plasmalogen生物合成的损伤。游离脂肪酸在ZP102细胞中的浓度是CHO-K1细胞的2倍，但其甲酯和三酰甘油在ZP102细胞中的浓度比对照细胞低。与对照细胞相比，ZP102细胞中CMH浓度显著升高，且两种细胞中脂肪酸分子种类，特别是脂肪酸饱和与不饱和脂肪酸的比例存在差异。[^<14>C]标记的饱和酸在ZP102细胞中的鞘磷脂（SM）和CMH的掺入率高于CHO-K1细胞。在从培养基中去除[^<14>C]木质素酸24小时后，加入细胞的木质素酸主要用于SM的合成。与CHO-K1细胞相比，ZP102细胞的膜迁移率较低。脂质代谢的改变，特别是饱和脂肪酸和鞘脂代谢的增强，可能与ZP102细胞膜流动性的降低有关，这与PBD中膜相关过程的功能障碍有关

项目成果

Alteration in the metastatic potential of ovarian cancer cells by transfect ion of the antisense gene of beta-1,4-galactosyltransferase.

通过转染β-1,4-半乳糖基转移酶反义基因改变卵巢癌细胞的转移潜力。

• 发表时间: 2003
• 期刊: Oncology Reports 10
• 作者: M.Nagura;M.Saito;M.Iwamori;Y.Sakakihara;T.Igarashi;Yamashita H.Kubushiro K.Ma J.Fujii T.Tsukazaki K.Iwamori M.Nozawa S.
• 通讯作者: Yamashita H.Kubushiro K.Ma J.Fujii T.Tsukazaki K.Iwamori M.Nozawa S.

Involvement of the C-terminal tail of Arthrobacter ureafaciens sialidase is enzyme M in cleavage of the internal sialic acid of ganglioside GM1

脲节杆菌唾液酸酶 M 的 C 末端尾参与神经节苷脂 GM1 内部唾液酸的裂解

• 发表时间: 2005
• 期刊: Journal of Biochemistry. 138(3):327-2005 138
• 作者: Iwamori M.Tanaka K.Kubushiro K.Lin B.Kiguchi K.Ishiwata I.Tsukazaki K.Nozawa;Iwamori M.Suzuki H.Ito N.Iwamori Y.Hanaoka K.;Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.;Iwamori M.Iwamori Y;Iwamori M.Kaido T.Iwamori Y.Ohta Y.Tsukamoto K.Kozaki S
• 通讯作者: Iwamori M.Kaido T.Iwamori Y.Ohta Y.Tsukamoto K.Kozaki S

Establishment of cells exhibiting mutated glycolipid synthesis from mouse thymus by immortalization with SV-40 virus

通过 SV-40 病毒永生化，建立显示小鼠胸腺糖脂合成突变的细胞

• 发表时间: 2005
• 期刊: Glycoconjugate Journal 22
• 作者: Iwamori M.Tanaka K.Kubushiro K.Lin B.Kiguchi K.Ishiwata I.Tsukazaki K.Nozawa;Iwamori M.Suzuki H.Ito N.Iwamori Y.Hanaoka K.;Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.;Iwamori M.Iwamori Y;Iwamori M.Kaido T.Iwamori Y.Ohta Y.Tsukamoto K.Kozaki S;Iwamori M.Iwamori Y
• 通讯作者: Iwamori M.Iwamori Y

Novel class of glycosphingolipids involved in male fertility.

参与男性生育能力的新型鞘糖脂。

• 发表时间: 2005
• 期刊: Journal of Biological Chemistry 280
• 作者: Iwamori M.Tanaka K.Kubushiro K.Lin B.Kiguchi K.Ishiwata I.Tsukazaki K.Nozawa;Iwamori M.Suzuki H.Ito N.Iwamori Y.Hanaoka K.;Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.
• 通讯作者: Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.

Establishment of cells exhibiting mutated glycolipid synthesis from mouse thymus by immortalization with SV-40 virus.

通过用 SV-40 病毒永生化，建立显示小鼠胸腺合成突变糖脂的细胞。

• 发表时间: 2005
• 期刊: Glycoconjugate Journal 22
• 作者: Iwamori M.;Iwamori Y.
• 通讯作者: Iwamori Y.