The UDP‐Galactose:Ceramide Galactosyltransferase: Expression Pattern in Oligodendrocytes and Schwann Cells During Myelination and Substrate Preference for Hydroxyceramide

Schaeren-Wiemers, Nicole; Bijl, P. van der; Schwab, Martin E.

doi:10.1046/j.1471-4159.1995.65052267.x

Cited by 85 publications

(50 citation statements)

References 35 publications

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“…Interestingly, 2-hydroxy ceramides are the preferred substrate for CGT over nonhydroxy ceramides (4,34,35). Other sphingolipids in myelin (sphingomyelin and complex glycolipids) do not normally contain 2-hydroxy fatty acids, even though the enzymes that synthesize these complex sphingolipids are not inherently incapable of incorporating 2-hydroxy substrates.…”

Section: Discussionmentioning

confidence: 99%

FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain

Alderson

Maldonado

Kern

et al. 2006

Journal of Lipid Research

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2-Hydroxy fatty acids are relatively minor species of membrane lipids found almost exclusively as N-acyl chains of sphingolipids. In mammals, 2-hydroxy sphingolipids are uniquely abundant in myelin galactosylceramide and sulfatide. Despite the well-documented abundance of 2-hydroxy galactolipids in the nervous system, the enzymatic process of the 2-hydroxylation is not fully understood. To fill this gap, we have identified a human fatty acid 2-hydroxylase gene (FA2H) that is highly expressed in brain. In this report, we test the hypothesis that FA2H is the major fatty acid 2-hydroxylase in mouse brain and that free 2-hydroxy fatty acids are formed as precursors of myelin 2-hydroxy galactolipids. The fatty acid compositions of galactolipids in neonatal mouse brain gradually changed during the course of myelination. The relative ratio of 2-hydroxy versus nonhydroxy galactolipids was very low at 2 days of age (z8% of total galactolipids) and increased 6-to 8-fold by 30 days of age. During this period, free 2-hydroxy fatty acid levels in mouse brain increased 5-to 9-fold, and their composition was reflected in the fatty acids in galactolipids, consistent with a precursor-product relationship. The changes in free 2-hydroxy fatty acid levels coincided with fatty acid 2-hydroxylase activity and with the upregulation of FA2H expression. Furthermore, mouse brain fatty acid 2-hydroxylase activity was inhibited by anti-FA2H antibodies. Together, these data provide evidence that FA2H is the major fatty acid 2-hydroxylase in brain and that 2-hydroxylation of free fatty acids is the first step in the synthesis of 2-hydroxy galactolipids.

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Section: Discussionmentioning

confidence: 99%

FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain

Alderson

Maldonado

Kern

et al. 2006

Journal of Lipid Research

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“…In skeletal muscle, the neutral GSLs and gangliosides were mostly in membrane vesicles with GlcCer predominating and only trace levels of LacCer ( 69,70 ). GalCer, sulfatide, and sphingomyelin are structural to myelin sheaths and are major lipids in oligodendrocytes and Schwann cells ( 71 ). In skin, ceramide comprises about 50% of total epidermal lipid and is generated from GlcCer in the lamellar bodies ( 72 ).…”

Section: Distribution and Functions Of Gslsmentioning

confidence: 99%

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Xu¹,

Barnes²,

Sun³

et al. 2010

Journal of Lipid Research

142

121

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important to a variety of cellular functions. GSLs and gangliosides are synthesized at the endoplasmic reticulum (ER) and are remodeled during transit from cis to trans Golgi by a series of glycosyl-and sialyl-transferases. These are then transported to the intracellular compartments and the plasma membrane where they become enriched in microdomains and membrane bilayers. During plasma membrane turnover, GSLs and gangliosides can be internalized and partially or completely degraded in the endosomal/lysosomal system to sphingosine and free fatty acids that are then transported or fl ipped across late endosomal and lysosomal membranes for recycling or for use as signaling molecules ( 2, 3 ). GSL metabolic pathwaysGSL biosynthesis begins with condensation of serine and palmitoyl-CoA catalyzed by serine-palmitoyltransferase (SPT) on the cytoplasmic face of the ER, leading to de novo biosynthesis of ceramide, the core of GSLs (

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“…Relatively large amounts of C18:0-sulfatide are present in neurons. In contrast, myelin is enriched in very-long-chain FA C22/C24-sulfatide ( 41,42 ). Alternatively, it has been suggested that sulfatide could be imported into neurons by apoE receptor-mediated endocytosis of sulfatide-containing apoE proteins ( 43 ).…”

Section: Kidneymentioning

confidence: 99%

“…COS cells are a sulfatide-defective cell line due to defective CGT activity ( 159 ). It has been suggested that sulfatide accumulation leads to a feedback inhibition of GalCer synthesis ( 41 ). We therefore transfected COS-7 cells with both CST and CGT genes from MDCK cells and established two cell clones that stably express sulfatide.…”

Section: Hivmentioning

confidence: 99%