Isolation and Characterization of a Novel Disialoganglioside Containing N-Glycolylneuraminic Acid from Pig Skeletal Muscle

Ariga, Toshio; Sekine, Michiko; Nakamura, Kyoko; Igarashi, Michihiro; Nagashima, Masaru; Miyatake, Tadashi; Suzuki, Akemi; Yamakawa, Tamio

doi:10.1093/jb/93.3.889

Cited by 11 publications

(4 citation statements)

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“…As NeuGc is not actively synthesized by human cells, Schauer (1985) suggested that the expression of NeuGc on human glycoconjugates may be derived from dietary sources. Indeed, bovine and porcine tissues, which are consumed by humans, contain significant amounts of NeuGc‐containing gangliosides (Yu and Ledeen, 1970; Ariga et al, 1983; Suzuki et al, 1985). It is therefore possible that the low levels of NeuGc found on human tumor glycoconjugates are derived exogenously from the diet.…”

Section: Discussionmentioning

confidence: 99%

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Ecsedy

Holthaus

Yohe

et al. 1999

Journal of Neurochemistry

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Ganglioside sialic acid content was examined in the U87-MG human glioma grown as cultured cells and as a xenograft in severe combined imunodeficiency (SCID) mice. The cultured cells and the xenograft possessed N-glycolylneuraminic acid (NeuGc)-containing gangliosides, despite the inability of human cells to synthesize NeuGc. Human cells express only N-acetylneuraminic acid (NeuAc)-containing gangliosides, whereas mouse cells express both NeuAc-and NeuGc-containing gangliosides. Small amounts of NeuGc ganglioside sialic acid (2-3% of total ganglioside sialic acid) were detected in the cultured cells, whereas large amounts (66% of total ganglioside sialic acid) were detected in the xenograft. The NeuGc in gangliosides of the cultured cells was derived from gangliosides in the fetal bovine serum of the culture medium, whereas that in the U87-MG xenograft was derived from gangliosides of the SCID host. The chromatographic distribution of U87-MG gangliosides differed markedly between the in vitro and in vivo growth environments. The neutral glycosphingolipids in the U87-MG cells consisted largely of glucosylceramide, galactosylceramide, and lactosylceramide, and their distribution also differed in the two growth environments. Asialo-GM1 (Gg4Cer) was not present in the cultured tumor cells but was expressed in the xenograft, suggesting an origin from infiltrating cells (macrophages) from the SCID host. The infiltration of mouse host cells and the expression of mouse sialic acid on human tumor cell glycoconjugates may alter the biochemical and immunogenic properties of xenografts. Key Words: Oligodendroglioma-Astrocytoma-N-Glycolylneuraminic acid-Brain tumor-Asialo-GM1.

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Section: Discussionmentioning

confidence: 99%

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Ecsedy

Holthaus

Yohe

et al. 1999

Journal of Neurochemistry

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“…The most common Neu5Gc-terminated glycolipid is the GM3 ganglioside with Neu5Gc linked to lactosylceramide (Iwamori and Nagai, 1978; Gasa and Makita, 1980; Hanagata et al, 1990). Complex Neu5Gc-containing gangliosides with several sialic acids have been identified (Ohashi and Yamakawa, 1977; Ariga et al, 1983; Nakao et al, 1991), also in various combinations with blood group ABO and Lewis antigen determinants (van Dessel et al, 1979; Nohara et al, 1990). Terminal sialic acid disaccharides exist in all the possible combinations NeuGc-NeuGc-, NeuAc-NeuAc-, NeuGc-NeuAc-, and NeuAc-NeuGc- (Watarai et al, 1991).…”

Section: General Aspects Of Glycoconjugates and Anti-carbohydrate Antmentioning

confidence: 99%

“…Studies on vascularized organs of pigs, the most likely species to be used for xenografting, are limited. However, Neu5Gc-containing gangliosides have been structurally characterized in porcine plasma (Hanagata et al, 1990), skeletal muscle (Ariga et al, 1983), adipose tissue (Ohashi and Yamakawa, 1977), peripheral nerve (Magnusson et al, 2005), small intestine (Diswall et al, 2007, 2014), kidney (Diswall et al, 2007), and pancreas (Nakamura et al, 1984; Diswall et al, 2007), and it can therefore be anticipated that Neu5Gc-terminated glycans are present in all porcine organs. Perhaps with the exception of the brain where Neu5Gc appears to be sparsely expressed (Davies and Varki, 2015).…”

Section: Structural Complexity and Species/tissue Distribution Of Neumentioning

confidence: 99%

The Structural Complexity and Animal Tissue Distribution of N-Glycolylneuraminic Acid (Neu5Gc)-Terminated Glycans. Implications for Their Immunogenicity in Clinical Xenografting

Breimer

Holgersson

2019

Front. Mol. Biosci.

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N -Glycolylneuraminic acid (Neu5Gc)-terminated glycans are present in all animal cells/tissues that are already used in the clinic such as bioprosthetic heart valves (BHV) as well as in those that potentially will be xenografted in the future to overcome end stage cell/organ failure. Humans, as a species lack this antigen determinant and can react with an immune response after exposure to Neu5Gc present in these products/cells/tissues. Genetically engineered source animals lacking Neu5Gc has been generated and so has animals that in addition lack the major αGal xenoantigen. The use of cells/tissues/organs from such animals may improve the long-term performance of BHV and allow future xenografting. This review summarizes the present knowledge regarding structural complexity and tissue distribution of Neu5Gc on glycans of cells/tissue/organs already used in the clinic or intended for treatment of end stage organ failure by xenografting. In addition, we briefly discuss the role of anti-Neu5Gc antibodies in the xenorejection process and how knowledge about Neu5Gc structural complexity can be used to design novel diagnostics for anti-Neu5Gc antibody detection.

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“…After the residue was washed with a small volume of methanol, the combined extract was centrifuged at 18,000 g for 20 min. The supernatant was evaporated to dryness under a stream of nitrogen, and the residue was dissolved in a small volume of C/M ( 1: 1 vol/vol), applied to a TLC plate, and developed with C/M/5 M N&OH/0.4% CaCI2.2H20 (6040:45 by volume; solvent A; Ariga et al, 1983) or with ethanol/l M C H 3 C O O m (3:2 vol/vol; solvent B Carey and Hirschberg, 1979). After drying, the plate was sprayed with 0.4% 2,5-diphenyloxazole (PFQ) in 2-methylnaphthalene containing 10% toluene (Bonner and Stedman, 1978) and exposed to a Kodak X A R J x-ray film at -7o'C.…”

Section: Tlc and Fluorographymentioning

confidence: 99%

A Ganglioside Species (G_D1α) Migrates at a Slow Rate and CMP‐Sialic Acid Severalfold Faster in Xenopus Sciatic Nerve: Fluorographic Demonstration

Igarashi

Komiya

Kurokawa

1986

Journal of Neurochemistry

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The ninth dorsal root ganglion of adult Xenopus laevis was labeled with N-acetyl-D-[6-3H]mannosamine, and intraaxonal migration of gangliosides was examined by analysis of the chloroform/methanol extract of each of 5-mm consecutive nerve segments by TLC coupled with fluorography. A unique disialoganglioside (GD1 alpha), which amounted to up to 83% of the total ganglioside in this nerve, migrated at 1-2 mm/day at 15 degrees C. This contrasts with the rapid transport of other ganglioside species previously reported in the optic systems of goldfish, rabbits, chickens, and rats. Fluorographic analysis also revealed a trichloroacetic acid-soluble substance migrating at a velocity of approximately 8 mm/day at 15 degrees C. The substance was considered to be CMP-sialic acid on the basis of observations that it comigrates with authentic CMP-N-acetylneuraminic acid in TLC developed with two different solvent systems, it is very labile to weak acid but resistant to neuraminidase from Vibrio cholerae, it is converted to N-acetylmannosamine when treated first with weak acid and subsequently with N-acetylneuraminic acid aldolase, and it has a beta-sialosyl group in its structure. Because CMP-sialic acid is believed to be the sole sialosyl donor in the cells, its migration in axons toward terminals, together with the previous demonstration of sialyltransferase activity in the synaptosomal plasma membrane, strongly supports the possibility that sialosylation of gangliosides and probably of other sialoglycoproteins is not confined to the Golgi apparatus, but can also occur after the compounds are committed to axonal transport.

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Isolation and Characterization of a Novel Disialoganglioside Containing N-Glycolylneuraminic Acid from Pig Skeletal Muscle

Cited by 11 publications

References 0 publications

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

The Structural Complexity and Animal Tissue Distribution of N-Glycolylneuraminic Acid (Neu5Gc)-Terminated Glycans. Implications for Their Immunogenicity in Clinical Xenografting

A Ganglioside Species (G_D1α) Migrates at a Slow Rate and CMP‐Sialic Acid Severalfold Faster in Xenopus Sciatic Nerve: Fluorographic Demonstration

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Isolation and Characterization of a Novel Disialoganglioside Containing N-Glycolylneuraminic Acid from Pig Skeletal Muscle

Cited by 11 publications

References 0 publications

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

The Structural Complexity and Animal Tissue Distribution of N-Glycolylneuraminic Acid (Neu5Gc)-Terminated Glycans. Implications for Their Immunogenicity in Clinical Xenografting

A Ganglioside Species (GD1α) Migrates at a Slow Rate and CMP‐Sialic Acid Severalfold Faster in Xenopus Sciatic Nerve: Fluorographic Demonstration

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A Ganglioside Species (G_D1α) Migrates at a Slow Rate and CMP‐Sialic Acid Severalfold Faster in Xenopus Sciatic Nerve: Fluorographic Demonstration