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Lipocalin‐type prostaglandin D synthase is up‐regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides
Author(s) -
Mohri Ikuko,
Taniike Masako,
Okazaki Issei,
KagitaniShimono Kuriko,
Aritake Kosuke,
Kanekiyo Takahisa,
Yagi Takashi,
Takikita Shoichi,
Kim HyungSuk,
Urade Yoshihiro,
Suzuki Kinuko
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03753.x
Subject(s) - sandhoff disease , krabbe disease , lipocalin , microglia , extracellular , biology , biochemistry , prostaglandin d2 , ganglioside , enzyme , leukodystrophy , prostaglandin , microbiology and biotechnology , chemistry , medicine , disease , immunology , inflammation
Lipocalin‐type prostaglandin (PG) D synthase (L‐PGDS) is a dually functional protein, acting both as a PGD 2 ‐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, GM 1 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 GM 1 and GM 2 gangliosides, accumulated in neurons in the course of LSD, with high affinities ( K D = 65 and 210 n m , respectively). This suggests that L‐PGDS may play a role in scavenging harmful lipophilic substrates in LSD.