Amounts Of GM2 Research Articles

Changes in the amounts of myelin lipids and molecular species of plasmalogen PE in the brain of an autopsy case with d-bifunctional protein deficiency

Changes in the molecular species of lipids associated with peroxisomal d-bifunctional protein (d-BP) deficiency were investigated in cerebral tissues to elucidate the pathological mechanisms underlying this disorder. Total phospholipids in the gray and white matters of the patient's brain were decreased to approximately 73% and 50% of control levels, respectively, and profound declines in myelin lipids, i.e. galactosyl ceramide and sulfatides, indicated dysmyelination in our patient with d-BP deficiency. Although the total ganglioside amounts in the gray and white matter of this patient's brain were also decreased to 61% and 37% of control levels and GM1 in the white matter was 20% of the control level, the relative amounts of GM2 in both the gray and the white matter of this patient's brain were increased in comparison to those in the control, indicating altered metabolism of gangliosides. In addition, among molecular species of phospholipids, plasmalogen-type and polyunsaturated fatty acid-containing phosphatidylethanolamine were characteristically decreased in the patient's gray matter. These alterations in the molecular species of brain lipids may affect sensitivity to oxidative stress and the membrane fluidity of neural cells, thereby producing the brain pathology of d-BP deficiency.

Gangliosides of melanoma.

The relationships between the ganglioside composition of melanomas and their biologic behavior were investigated. (1) The amount of GM2 and/or GD2 in melanoma cells injected into nude mice correlated with the tumor growth rate. (2) GD2 content of melanoma cell lines correlated with sensitivity to radiation and vincristine. (3) GM2 expression of melanoma cells correlated with sensitivity to lymphokine-activated killer cells. (4) Gangliosides inhibited the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. Based on these results, we proposed a hypothesis for the role of melanoma-associated gangliosides in the biologic behavior of melanomas and suggested a prospective melanoma treatment related to the gangliosides.

Two Pathways for GM2(NeuGc) Expression in Mice: Genetic Analysis1

We have reported that WHT/Ht mice express neither GM2(NeuGc) nor GM1(NeuGc) in the liver or erythrocytes due to a defect on the Ggm-2 gene, which was demonstrated to control the activity of UDP-GalNAc:GM3(NeuGc) N-acetylgalactosaminyltransferase in mouse liver, and, in addition, WHT/Ht mice do not express a detectable amount of GM2(NeuGc) but do express GM1(NeuGc) in tissues other than the liver and erythrocytes, such as the spleen, thymus, heart, lung, kidney, and testis [Nakamura et al. (1988) J. Biochem. 103, 201-208]. In order to determine whether the phenotype of WHT/Ht mice exhibiting an undetectable amount of GM2(NeuGc) in these tissues is genetically controlled or not, we analyzed the expression of gangliosides in the progeny obtained on backcross mating between (BALB/c X WHT/Ht)F1 and WHT/Ht mice, and in a GM2(NeuGc) congenic mouse, WHT.C. Concerning the expression of GM2(NeuGc) in the liver, lung, and kidney, 102 backcross mice could be segregated into two types. One type expressed a detectable amount of GM2(NeuGc) in the liver, lung, and kidney, and the other type did not. The ratio of the numbers of mice exhibiting these two types was 42: 60, indicating that the two phenotypes were genetically determined by the involvement of a single autosomal gene. Recombination as to GM2(NeuGc) expression in the liver, lung, and kidney was not detected among the 102 backcross mice. Analysis of the GM2(NeuGc) congenic mouse indicated that a detectable amount of GM2(NeuGc) was expressed in the liver, erythrocytes, lung, kidney, heart, spleen, and small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Ganglioside GM2 expression on human melanoma cells correlates with sensitivity to lymphokine-activated killer cells.

Ganglioside GM2 is expressed on cell surface membranes of a variety of human malignant cells and has been demonstrated to be immunogenic in humans. We have assessed the role of the antigen GM2 on melanoma cells as a recognition structure for lymphokine-activated killer (LAK) cells. LAK cells were generated by stimulation of non-adherent peripheral blood lymphocytes (PBL) from human donors with recombinant interleukin-2 (IL-2). The selection of target cells was based on GM2 content and included 11 human melanoma cell lines and 2 human leukemia lines. Using a single-cell binding assay, LAK cell binding to target lines expressing high levels of GM2 was significantly greater than to those expressing minimum GM2. This cell-binding was specifically inhibited by addition of purified GM2 but not by other gangliosides. LAK-melanoma cell-binding was also specifically inhibited by anti-GM2 monoclonal antibody (MAb). For further analysis LAK cell lysis of melanoma target cells expressing various amounts of GM2 was assessed. A significant correlation occurred with GM2 expression and LAK cell lysis (p less than 0.025; r = 0.623). Three other gangliosides commonly expressed on human melanoma, GM3, GD3 and GD2, had no correlation with LAK cell lysis. These studies suggest that GM2 on melanoma cells is a marker for LAK cell sensitivity, as well as indicate that GM2 is a potential target recognition structure for human LAK cells.

GANGLIOSIDE1−COMPOSITION OF BRAIN IN TAY‐SACHS DISEASE: INCREASED AMOUNTS OF GD2 AND N‐ACETYL‐β‐D‐GALACTOSAMINYL GD1a GANGLIOSIDE

Abstract— The ganglioside composition of the brain of a patient with Tay‐Sachs disease (TS‐brain) was determined by a newly developed ganglioside‐mapping procedure and compared with that of an age‐matched control brain. GM2 ganglioside was the predominant component in TS‐brain and the following gangliosides were also found, GM1, GD1a, GD1b and GT1 (major gangliosides in normal brain), and GM3, GD3, GD2 and GD1a‐GAN (minor or undetectable components of normal brain). Individual gangliosides were isolated by column chromatography using a combination of DEAE‐Sepharose, Iatrobeads and Silica Gel 60 and their structures were confirmed by comparing them with authentic standards using TLC, analysing their carbohydrate compositions by gas‐liquid chromatography and cleaving them sequentially with glycosidases. The amounts of individual components were measured by quantitative densitometric scanning of the thin‐layer plates. As a reflection of myelin breakdown, no sialosylgalactosyl ceramide was detectable in TS‐brain. Although the total amounts of all gangliosides except GM2 in TS‐brain were low, there were normal molar ratios of the main gangliosides in normal brain, that is, GM1, GD1a, GD1b and GT1. In comparison with the amount of GDla ganglioside, the amounts of GM2, GD2 and GD1a‐GAN, which contain N‐acetylgalactosamine as a terminal carbohydrate residue, were all elevated in TS‐brain. The long chain bases of individual gangliosides contained both C‐18 and C‐20 sphingosine in different ratios and the ratio of C‐20 to C‐18 increased in the gangliosides in the order: GM2 < GM1 < GD1a < GD1a‐GAN < GD1b < GT1 in both normal brain and TS‐brain. In contrast, GD2 and GD3 gangliosides consisted mainly of C‐18 sphingosine. The C‐20 to C‐18 ratios of individual gangliosides in the TS‐brain were lower than those of age‐matched control brain.Hexosaminidase from Turbo cornutus showed the same specific activity and Km value in catalysing the cleavage of terminal N‐acetylgalactosaminyl residues from GM2, GD2 and GD1a‐GAN, suggesting that the brain gangliosides that increase in Tay‐Sachs disease may be cleaved by the same enzyme.