Lipocalin‐type prostaglandin D synthase is up‐regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides
Lipocalin‐type prostaglandin D synthase is up‐regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides
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DOI：
10.1111/j.1471-4159.2006.03753.x
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发表时间：
2006-05
影响因子：
4.7
通讯作者：
I. Mohri;M. Taniike;Issei Okazaki;Kuriko Kagitani-Shimono;K. Aritake;T. Kanekiyo;T. Yagi;S. Takikita;Hyung-Suk Kim;Y. Urade;Kinuko Suzuki
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文献类型：
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作者：
I. Mohri;M. Taniike;Issei Okazaki;Kuriko Kagitani-Shimono;K. Aritake;T. Kanekiyo;T. Yagi;S. Takikita;Hyung-Suk Kim;Y. Urade;Kinuko Suzuki
脂质运载蛋白型前列腺素（PG）D合成酶（L-PGDS）是一种双重功能蛋白，既作为PGD 2合成酶，又作为各种亲脂性小分子的细胞外转运蛋白。L-PGDS在中枢神经系统中的少突胶质细胞（OL）中表达，并在球样细胞脑白质营养不良（克拉伯病）模型ticker小鼠的OL中上调。我们使用Tay-Sachs病、Sandhoff病、GM 1神经节苷脂沉积症和Niemann-Pick C1型疾病的LSD小鼠模型，研究了L-PGDS的上调是否是Krabbe病所特有的，或者是溶酶体贮积症（LSD）中更普遍的现象。定量RT-PCR显示，所有这些小鼠模型的脑中L-PGDS mRNA均上调。此外，在OL中观察到强L-PGDS免疫反应性，但在这些模型中的星形胶质细胞或小胶质细胞中均未观察到。因此，L-PGDS的上调似乎是LSD中OL的常见反应。此外，表面等离子体共振分析显示，L-PGDS结合GM 1和GM 2神经节苷脂，在LSD过程中积累在神经元中，具有高亲和力（KD分别为65和210 nm）。这表明L-PGDS可能在清除LSD中有害的亲脂性底物方面发挥作用。
Lipocalin‐type prostaglandin (PG) D synthase (L‐PGDS) is a dually functional protein, acting both as a PGD2‐synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. L‐PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up‐regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease). We investigated whether up‐regulation of L‐PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay–Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann–Pick type C1 disease. Quantitative RT‐PCR revealed that L‐PGDS mRNA was up‐regulated in the brains of all these mouse models. In addition, strong L‐PGDS immunoreactivity was observed in OLs, but not in either astrocytes or microglia in these models. Thus, up‐regulation of L‐PGDS appears to be a common response of OLs in LSDs. Moreover, surface plasmon resonance analyses revealed that L‐PGDS binds GM1 and GM2 gangliosides, accumulated in neurons in the course of LSD, with high affinities (KD = 65 and 210 nm, respectively). This suggests that L‐PGDS may play a role in scavenging harmful lipophilic substrates in LSD.