Disease relevance of galactosylceramide

• Here we show that primary intestinal (jejunal) epithelial cells express galactosylceramide, an alternative primary receptor for HIV-1, and CCR5 but not CXCR4 [1].
• We also present evidence that a galactosylceramide-like compound is present on the sperm membrane and could function as an alternative receptor for HIV [2].
• In the patients with the chronic progressive form of multiple sclerosis, galactosylceramide remained undetectable [3].
• In the patients with relapsing-remitting multiple sclerosis, there was a good correlation between the elevation of serum galactosylceramide levels and clinical relapses [3].
• Galactosylceramide lipidosis: novel presentation as a slowly progressive spinocerebellar degeneration [4].

High impact information on galactosylceramide

• During the chase period, radioactivity was increased at plasma membrane plus Golgi as phospholipids and no accumulation of GalCer or Cer was found in lysosome [5].
• During vertebrate development, oligodendrocytes wrap their plasma membrane around axons to produce myelin, a specialized membrane highly enriched in galactosylceramide (GalC) and cholesterol [6].
• On a nanoscale resolution, using stimulated emission depletion and fluorescence resonance energy transfer microscopy, we demonstrated a neuronal-dependent clustering of GalC in oligodendrocytes [6].
• Here, we report that the lipid metabolite psychosine (galactosylsphingosine), derived from galactosylceramide, induced formation of multinuclear cells from a variety of nonadherent and adherent cells due to inhibition of cytokinesis [7].
• Formation of a cholesterol- and galactosylceramide-rich membrane domain (myelin rafts) may be critical for the sorting of PLP and assembly of myelin in oligodendrocytes [8].

Chemical compound and disease context of galactosylceramide

• In the present study, we investigated the mechanisms of action of SPC3 in these cell types--i.e., CD4+ lymphocytes and CD4- epithelial cells expressing galactosylceramide (GalCer), an alternative receptor for HIV-1 gp120 [9].
• In mucinous cystadenocarcinoma, galactosylceramide is found in the relatively high concentration and is also composed of N-cerebronoyl phytosphingosine [10].
• We found that HIV-1 recombinant gp120 (IIIB isolate) could penetrate into a monomolecular film of alpha-hydroxylated galactosylceramide (GalCer-HFA), while ceramides, GluCer, and nonhydroxylated GalCer were totally inactive [11].
• Synthetic soluble analogs of galactosylceramide (GalCer) bind to the V3 domain of HIV-1 gp120 and inhibit HIV-1-induced fusion and entry [12].
• OBJECTIVE: To detect the expression CXCR4/fusin in human intestinal epithelial cells and to assess its potential role in the pathway of HIV-1 infection mediated by the alternative gp120 receptor galactosylceramide (GalCer) [13].

Biological context of galactosylceramide

• The crude activator preparation from normal urine was also found to stimulate the hydrolysis of galactosylceramide sulfate by arylsulfatase A [14].
• The reduced galactosylceramide in the brain of the double knockout mice and the significantly higher psychosine in the brain of the galc(-/-), bgal(+/-) mice cannot readily be explained from the genotypes of these mice [15].
• The brain inexplicably contains only a half-normal amount of galactosylceramide, which may account for the mild clinical and pathological phenotype [15].
• Galactosylceramide as a bilayer component is not essential for lipid mobilization by Sap-A, which requires intact disulfide bridges for activity [16].
• We also observed that pretreating cells with galactosylceramide (GalCER) significantly inhibited DNR-induced apoptosis [17].

Anatomical context of galactosylceramide

• We examined the uptake and intracellular transport of the fluorescent glucosylceramide analogue N-[5-(5,7-dimethyl BODIPYTM)-1-pentanoyl]-glucosyl sphingosine (C5-DMB-GlcCer) in human skin fibroblasts, and we compared its behavior to that of the corresponding fluorescent analogues of sphingomyelin, galactosylceramide, and lactosylceramide [18].
• Remarkably, in Caco-2 cells GalCer and GlcCer displayed the same apical/basolateral polarity, but it was sixfold lower for lipids with a C6OH chain than for C6-NBD lipids [19].
• These observations are consistent with the transbilayer movement of fluorescent analogues of glucosylceramide and galactosylceramide at the plasma membrane and early endosomes of human skin fibroblasts, and suggest that both endocytic and nonendocytic pathways are used in the internalization of these lipids from the plasma membrane [18].
• Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism [20].
• Recent studies showed that antibodies recognizing a neutral glycolipid related to galactosylceramide (GalCer) in HT-29 cells inhibited HIV-1 infection of this cell line, extending previous findings in neural cells [21].

Associations of galactosylceramide with other chemical compounds

• In control skin fibroblasts, CS was transported to lysosome and metabolized there to galactosylceramide (GalCer) and ceramide (Cer) within 1 h [5].
• We show that a ceramide containing the 2-hydroxy fatty acid C6OH was preferentially converted by MDCK and Caco-2 cells to galactosylceramide (GalCer) and its derivatives galabiosylceramide (Ga2Cer) and sulfatide (SGalCer) as compared to SM and GlcCer--all endogenous lipid classes of these cells [19].
• Calcium has been shown previously to cause aggregation of phosphatidylcholine/cholesterol liposomes containing galactosylceramide (GalCer) with similar liposomes containing cerebroside sulfate (galactosylceramide I3 sulfate) (CBS), suggesting that it mediates a carbohydrate-carbohydrate association between these two glycolipids [22].
• Antibody 1D6 completely blocked the binding of SP-A to dipalmitoylphosphatidylcholine and galactosylceramide and liposome aggregation [23].
• The transition temperature of DPPC, galactosylceramide, and asialo-GM1 is affected little by MBP while their transition enthalpy is decreased in proportion to the amount of protein in the mixture [24].

Gene context of galactosylceramide

• GALC is responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon [25].
• NB express no CD4 and low levels of galactosylceramide or nucleolin [26].
• Neither of these cell lines expresses surface CD4; however, both express the alternative epithelial receptor galactosylceramide and the coreceptor CXCR4 [27].
• Lipid analysis revealed that the PLP-MBP-S-MAG coimmunoprecipitated with some phospholipids and sulfatide but not cholesterol or galactosylceramide [28].
• A galactosylceramide binding domain is involved in trafficking of CLN3 from Golgi to rafts via recycling endosomes [29].

Analytical, diagnostic and therapeutic context of galactosylceramide

• The oligodendrocytes selected in this way were characterized by: (i) morphology, (ii) immunofluorescence labeling by antibodies to myelin basic protein and galactosylceramide, and (iii) biochemical analyses for myelin basic protein, activity of 2',3'-cyclic-nucleotide 3'-phosphohydrolase, and sulfogalactosylceramide synthesis [30].
• Investigation of the calcium-mediated association between the carbohydrate head groups of galactosylceramide and galactosylceramide I3 sulfate by electrospray ionization mass spectrometry [22].
• Tumors produced by subcutaneous injection of these cell lines into C57BL/6 mice were also unique in that they contained high levels of both sulfatide and galactosylceramide [31].
• Relative to K-12 (K88-), the K-12 (K88+) bacterial cells bound more avidly to galactosylceramide when the neutral lipids were separated on thin-layer chromatography plates [32].
• As determined by freeze fracture electron microscopy, increasing levels of bovine brain galactosylceramide (GalCer) altered the surface structure of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers by inducing a striking "macro-ripple" phase in the larger, multilamellar lipid vesicles at GalCer mole fractions between 0.4 and 0 [33].

References