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

进行了这项研究以确定过氧化物体生物发生疾病中脂质组成和代谢的变化。在ZS患者的大脑皮层中，与各种年龄的对照水平相比，神经酰胺单己糖苷（CMH）和胆固醇酯（CE）的量增加。尽管CMH在白质中随着年龄的增长而积累，但ZS中识别出CMH的增加。对PC的分子物种加PS的分数分析表明，Zs的脑皮质中偶极甲酰基甘油磷脂的显着增加。我们还分析了ZP102细胞缺陷过氧组中脂质组成，并表现出脂肪酸的过氧化物体β-氧化和血浆基因生物合成的损害。 ZP102细胞中游离脂肪酸的浓度是CHO-K1细胞中的两倍，但是与对照细胞相比，ZP102细胞中其甲基酯和三酰基甘油含量减少了。同样，与对照细胞中的CMH相比，ZP102细胞中CMH的浓度显着增加，并且在两种细胞类型之间，脂肪酸分子物种，尤其是单个脂质的饱和和不饱和的单个脂质的比率有所不同。在ZP102细胞中，标记为鞘磷脂（SM）和CMH的[^<14> C]的掺入酸的速率高于CHO-K1细胞中的酸。在从培养基中去除[^<14> c]木质酸后，将掺入细胞中的木质酸主要用于在24小时合成SM。与CHO-K1细胞相比，ZP102细胞显示出较低的膜迁移率。脂质代谢的改变特别是增强的饱和脂肪酸和鞘脂的代谢可能与ZP102细胞的膜流动性降低有关，这在PBD中膜连接过程的功能障碍暗示

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.

Tissue-specific loss of fucosylated glycolipids in mice with targeted deletion of alpha(1,2)fucosyltransferase genes.

通过靶向删除 α(1,2) 岩藻糖基转移酶基因，小鼠中岩藻糖基化糖脂的组织特异性损失。

• 发表时间: 2004
• 期刊: Biochemical Journal 380(Pt1)
• 作者: Iwamori M.;Domino SE.
• 通讯作者: Domino SE.

Alteration in the metastatic potential of ovarian cancer cells by transfection 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(6)
• 作者: Yamashita H.;Kuboshiro K.;Ma J.;Fujii T.;Tsukazaki K.;Iwamori M.;Nozawa S.
• 通讯作者: Nozawa 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

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