Studies on goat brain gangliosides: Immunogenicity & specificity of different gangliosides.
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Animals↗
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Gangliosides and Guillain-Barré syndrome. Science supports the use of gangliosides.
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Gangliosides↗
[Discovery of a novel bioactivity of gangliosides: gangliosides as differentiation-inducers for human leukemic cells and mechanism(s) of their action].
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Animals↗
The biosynthesis of brain gangliosides--evidence for a "transient pool" and an "end product pool" of gangliosides.
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Animals↗
[Function analysis of complex gangliosides by gangliosides-lacking mutant mice].
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Animals↗
Isolation and characterization of gangliosides from Theileria sergenti.
The gangliosides of Theileria sergenti piroplasms were isolated and analyzed by thin-layer chromatography (TLC) and TLC immunostaining test. Four species of gangliosides, designated as G-1, G-2, G-3, and G-4, were separated on TLC. G-1, G-2, G-3, and G-4 ganglioside showed the same mobility as GM3, sialosylparagloboside (SPG), i-active ganglioside, and I-active ganglioside on the TLC plate, respectively. In order to characterize the molecular species of gangliosides from T. sergenti, G-1, G-2, G-3, and G-4 gangliosides were purified and tested by TLC immunostaining test with monoclonal antibodies against gangliosides. G-1 ganglioside had reactivity to anti-GM3 monoclonal antibody. G-2 gave reaction with monoclonal antibody to SPG containing N-glycolylneuraminic acid (NeuGc). G-3 showed reactivity to the anti-i-active ganglioside (NeuGc) monoclonal antibody. G-4 was recognized by the monoclonal antibody which reacts with I-active ganglioside (NeuGc). In addition, sialic acid moiety of the gangliosides from T. sergenti piroplasms was also analyzed. N-acetylneuraminic acid-containing gangliosides were hardly detectable in T. sergenti piroplasms. Gangliosides from T. sergenti (G-1, G-2, G-3, and G-4) carried only NeuGc as their sialic acid moiety. These results suggest that G-1, G-2, G-3, and G-4 gangliosides are GM3 (NeuGc) [NeuGc alpha 2-3Gal beta 1-4Glc beta 1-Cer], SPG (NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], i-active ganglioside (NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], and I-active ganglioside(NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3 (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6) Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], respectively.
Anemia↗
Correlation of gangliosides GM2 and GM3 with metastatic potential to lungs of mouse B16 melanoma.
Ten B16 mouse melanoma cell lines with increasing metastatic potential to lungs (B16LuF1 to B16LuF10) were generated by in-vitro & in-vivo selection technique starting with B16F1 melanoma cell line. The number of metastatic tumor nodules in lungs rose with increasing metastatic potential. Tumor cell gangliosides of B16LuF1 to B16LuF10 cell lines, analysed and compared with TLC, showed eight major ganglioside bands. Band1 to band6 corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively. Band7 and Band8 could not be identified. The concentration of total as well as individual ganglioside bands of B16LuF1 to B16LuF10 cells appeared to rise with increasing metastatic potential. Gangliosides from the plasma of these cell lines (B16LuF1 to B16LuF10) maintained in-vivo in C57BL/6 mice on TLC analysis gave eight major ganglioside bands, similar to those of cells. Plasma gangliosides appeared to rise with increasing metastatic potential. However, it was interesting to see that only band5 and band6 gangliosides in plasma increased almost linearly with increasing metastatic potential. The remaining six ganglioside bands in the plasma did not show such correlation. Band5 and Band6 gangliosides corresponded with standard gangliosides GM2 and GM3 respectively. Gangliosides of the spent culture media, secreted by these cell lines in-vitro in tissue culture also gave eight major ganglioside bands, similar to that of cells. Spent culture media gangliosides appeared to increase with increasing metastatic potential. However, concentration of only band5 and band6 gangliosides of spent culture media increased almost linearly with increasing metastatic potential, thus further confirming the role of band5(GM2) and Band6(GM3) gangliosides in regulating metastatic potential of B16-melanoma cells to lung.
Animals↗
Gangliosides and autoimmune diabetes.
Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin-dependent (type 1) diabetes mellitus. This last disease is caused by the autoimmune destruction of insulin-producing pancreatic islet cells in genetically predisposed individuals. Autoantibodies and T lymphocytes directed towards multiple islet autoantigens have been detected in the circulation, well before the clinical onset of the disease, in a prodromal phase during which pancreatic islet beta-cells are presumably destroyed. Among the target autoantigens, some are of protein nature but others are acidic glycolipids such as sulphatides158 and the gangliosides GT3, GD3 and especially GM2-1. This last component is specifically expressed in pancreatic islets and has been shown to represent a target of IgG autoantibodies highly associated with diabetes development in first-degree relatives of type 1 diabetic individuals. In addition, the GM2-1 ganglioside appears to be one of the antigens recognized by cytoplasmic ICA, a heterogeneous group of antibodies which specifically react with islets on pancreatic frozen sections. In conclusion, studies performed in the last decade have clearly indicated that gangliosides represent a heterogeneous class of molecules that are involved in several cellular processes that are of crucial importance in physiological as well as in pathological conditions. Interestingly, these molecules, despite their small size, have been shown to represent not only important antigens in tumour immunology but are also able to elicit a specific autoimmune response, thus representing important autoantigens in some autoimmune disorders. It is of interest that, in addition to neurological autoimmune disorders where autoimmunity to gangliosides is frequent and usually of considerable magnitude, an autoimmune response to this class of molecules has been observed in autoimmune diabetes. (ABSTRACT TRUNCATED)
Autoantigens↗
Neuroimmunology of gangliosides in human neurons and glial cells in culture.
Gangliosides (sialic-acid-bearing glycolipids) have received attention in recent years because of their role in cell recognition phenomena, synaptic transmission, memory generation, and nerve regeneration in the fields of neurosciences. It is suggested that each brain region or each neural cell type may contain a specific and characteristic set of gangliosides. We have investigated the immunocytochemical localization of several classes of gangliosides that include GM1, GM4, GD3, and GQ gangliosides on the cell surface of various cell types found in human neural cell cultures with antibodies specific for these gangliosides. Cell cultures were obtained from adult human brains and fetal human dorsal root ganglia and spinal cord and cultured in vitro for the period up to 6 months and utilized for the ganglioside immunocytochemistry. It was demonstrated that GM1 ganglioside was present in all galactocerebroside-positive oligodendrocytes and most of glial fibrillary acid protein (GFAP)-positive astrocytes (80%), most of neurofilament-positive neurons (80%), 50-70% of Schwann cells, and 5-10% of fibronectin-positive fibroblasts; GM4 ganglioside could be detected in all oligodendrocytes, 80% of astrocytes, and 50% of Schwann cells, while no staining was found in neurons or fibroblasts; GD3 ganglioside was present in all oligodendrocytes and 5-10% of astrocytes but not in neurons, Schwann cells, or fibroblasts; and all of fetal CNS neurons and approximately 80-90% of fetal dorsal root ganglia (DRG) neurons and a small percentage of astrocytes (10-20% in fetal and less than 1% in adult astrocytes) was labeled by A2B5 antibody which is specific for GQ ganglioside, while this antibody did not stain cell surface of oligodendrocytes, Schwann cells, or fibroblasts. Three classes of gangliosides, GM1, GM4, and GD3 were found to be definite components of fetal and adult human oligodendroglial plasma membrane, while GM1 and GM4 gangliosides were detected on the surface of most astrocytes. Only a minor population of astrocytes from both fetal and adult human CNS contained GD3 and GQ gangliosides. Two classes of gangliosides, GM1 and GQ, were detected on the surface of fetal human neurons. More than half of fetal Schwann cells reacted to GM1 and GM4 antibodies but did not to GD3 or GQ antibodies. We recognized the presence of a specific and characteristic set of gangliosides on the cell surface of different human neural cell types and these findings should facilitate further investigation of the precise biological activity of these gangliosides.
Aged↗
Ganglioside GM3 inhibits the high glucose- and TGF-beta1-induced proliferation of rat glomerular mesangial cells.
Abrupt proliferation of glomerular mesangial cells (GMCs) is a common feature in the early stage of diabetic glomerulopathy, and ganglioside GM3 (NeuAcalpha3Galbeta4Glcbeta1Cer) is thought to regulate the proliferation of many cell types. Recently, we have reported ganglioside GM3 as a modulator of glomerular hypertrophy in streptozotocin-induced diabetic rats []. This study examined whether modulation of cellular ganglioside GM3 could regulate the high glucose- and transforming growth factor-beta1 (TGF-beta1)-induced proliferation of GMCs. To pharmacologically modulate the cellular ganglioside GM3, GMCs originated from rat kidneys were cultured with exogenous ganglioside GM3 or d-threo-PDMP, an inhibitor of ganglioside synthesis, in the RPMI 1640 media containing normal (5.6 mM, NG) or high (25 mM, HG) glucose. HG, TGF-beta1 (10 ng/ml) and d-threo-PDMP (20 microM) significantly stimulated the mesangial cell proliferation, whereas these increments were remarkable attenuated by exogenous ganglioside mixture (0.1-0.2 mg/ml) or GM3 (20-100 microM) in a dose-dependent manner. The mesangial cell proliferation caused by HG, TGF-beta1 and d-threo-PDMP was closely correlated with decreases in both cellular sialic acid contents and ganglioside GM3 synthase activity. Based upon the mobility on high-performance thin-layer chromatography (HPTLC), GMCs showed a complex pattern of ganglioside expression that consisted, at least, of five different components of gangliosides, mainly ganglioside GM3. HG, TGF-beta1 and d-threo-PDMP induced a significant reduction of ganglioside expression with apparent changes in the composition of ganglioside GM3, and semi-quantitative analysis by HPTLC showed that ganglioside GM3 expression reduced to about 35-54% of control. These results provide a pathophysiological link between mesangial cell proliferation and ganglioside GM3 expression, indicating that exogenously added ganglioside GM3 inhibits the high-ambient glucose- and TGF-beta1-induced proliferation of cultured GMCs.
Animals↗
Exogenous gangliosides and Guillain-Barré syndrome. An observational study in the local health district of Ferrara, Italy.
A retrospective study was carried out in the Ferrara Local Health District, Italy, for the period 1981-1993 (average resident population: 177,235 inhabitants) to establish whether people exposed to exogenous gangliosides had a higher risk of Guillain-Barré syndrome. The incidence of Guillain-Barré syndrome of 1.9/100,000 population/year [95% confidence interval (CI): 1.3-2.5] reported in Ferrara Local Health District in the same period was used as a reference for comparison. The data bank of Ferrara Local Health District made it possible, first to estimate the number of individuals exposed to gangliosides in the resident population of Ferrara Local Health District (3.7%), the number of ganglioside prescriptions and the number of cases of Guillain-Barré syndrome who had treatment with gangliosides (nine patients, 20.9%), and, secondly, to verify the sequence of events between the ganglioside injection and the onset of the disease. Seven of the nine patients (77.8%) received gangliosides as treatment for peripheral neuropathy (Guillain-Barré syndrome onset before gangliosides were prescribed). For the other two patients (22.2%) a possible appropriate temporal sequence between ganglioside injection and onset of Guillain-Barré syndrome was found. Based on two possible ganglioside-related cases, the risk of Guillain-Barré syndrome was higher in the exposed (0.53/100,000 population/month following ganglioside injection; 95% CI: 0.06-1.91) compared with the unexposed population, but the difference was not significant. When only individuals prescribed with mixed gangliosides were considered (both possible ganglioside-related Guillain-Barré syndrome cases received mixed gangliosides), the risk of Guillain-Barré syndrome was higher (0.64/100,000 population/month following ganglioside injection; 95% CI: 0.08-2.31) but the difference from the risk in unexposed individuals was not statistically significant. The relative risk for the exposure to mixed gangliosides was borderline (relative risk = 4.3; 95% CI: 1.0-17.8). The wide 95% confidence intervals were a consequence of sample size limitations. Considering also that the exposed and unexposed groups differed in age (those exposed were older than those unexposed and the age-specific incidence of Guillain-Barré syndrome in the study population increased with increasing age), the present findings question either a strong increased risk of Guillain-Barré syndrome in people exposed to exogenous gangliosides or an immunogenic role of these agents in humans. However, because of the limited sample size, the results are not conclusive.
Adolescent↗
Distribution of exogenously added gangliosides in serum proteins depends on the relative affinity of albumin and lipoproteins.
Gangliosides in normal serum are found only in lipoproteins and the relative content of the three major lipoprotein fractions is low density lipoprotein > high density lipoprotein > very low density lipoprotein (LDL > HDL > VLDL). Upon in vitro incubation of labeled gangliosides with human serum, about 15% of the exogenous gangliosides became associated with the albumin fraction and 85% were distributed on the lipoproteins in the order HDL > LDL > VLDL. To compare the relative affinities of serum proteins for gangliosides, the levels of exchange of exogenous gangliosides between preloaded serum proteins were determined. Although albumin had the highest binding capacity for gangliosides, 85% of the albumin-loaded gangliosides were transferred to the total lipoprotein fraction and this exchange was reversible. The transfer rate from albumin to isolated lipoproteins was higher to LDL (90%) and HDL (85%) whereas only 55% of albumin-loaded gangliosides were transferred to VLDL. The study of exchanges of preloaded gangliosides between isolated lipoproteins showed that the extent of transfer of gangliosides from a given lipoprotein fraction onto other lipoproteins was inversely correlated with its endogenous ganglioside content. Moreover, in the absence of albumin from the incubation medium, the final lipoprotein distribution of remaining exogenous gangliosides was similar to the normal distribution of endogenous gangliosides in serum lipoproteins. The formation of unexchangeable complexes between albumin and micellar exogenous gangliosides could be a possible explanation for the observed differences in the distribution of exogenous and endogenous gangliosides in serum proteins.
Blood Proteins↗
Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion to collagen.
Gangliosides, sialic acid-containing glycosphingolipids, accumulate in atherosclerotic vessels. Their role in the pathogenesis of atherosclerosis is unknown. Gangliosides isolated from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion and enhance platelet adhesion to immobilized collagen. These activities are all mediated by ganglioside effects on the platelet integrin collagen receptor alpha2beta1. Therefore, we hypothesized that gangliosides isolated from atherosclerotic plaques would enhance platelet adhesion to immobilized collagen, a major component of the subendothelial matrix of blood vessels. Furthermore, we questioned whether this effect of atherosclerotic gangliosides might play a role in the pathogenesis of atherosclerosis. To test this hypothesis, we isolated the gangliosides from postmortem aortas of patients with extensive atherosclerotic disease and examined their effects on platelet adhesion. Samples of aortic tissue taken from areas involved with atherosclerotic plaque demonstrated accumulation of gangliosides (64.9+/-6.5 nmol/g wet weight) compared with gangliosides isolated from control normal aortic tissue taken from children who died of noncardiac causes (NAGs; 21.1+/-6.4 nmol/g wet weight). Interestingly, samples of tissue taken from diseased aortas but from areas not involved with gross plaque formation also demonstrated ganglioside accumulation (47.6+/-12.8 nmol/g wet weight). Next, the activity of each of these gangliosides on platelet adhesion to immobilized type I collagen was studied. Atherosclerotic aortic gangliosides (AAGs) as well as those isolated from grossly unaffected areas of the same aorta (UAGs) both increased platelet adhesion compared with control NAGs (OD570, 0. 37+/-0.11 and 0.29+/-0.14 versus 0.16+/-0.07, respectively; P<0.01 and P<0.05, respectively). These OD570 values corresponded to 9x10(5), 8x10(4), and 6x10(3) platelets per well after preincubation with 5 micromol/L AAG, UAG, and NAG, respectively. Increased adhesion was observed after preincubation with as little as 0.5 micromol/L AAG, and maximal adhesion was seen at 2.5 micromol/L, with a plateau extending to the highest concentration tested, 10 micromol/L. The effect of AAGs on platelet adhesion to collagen was abrogated by incubation of treated platelets with F-17 anti-alpha2 monoclonal antibody (OD570, 0.13+/-0.02). Finally, the effects of the major individual gangliosides isolated from atherosclerotic tissues, GM3 and GD3, were tested. GM3 increased adhesion to collagen (OD570, 0.415+/-0.06) as did GD3 (0.31+/-0.08). Similar to that of AAGs, the effect of both molecules was blocked by F-17 (0. 09+/-0.04 and 0.13+/-0.06, respectively). These experiments demonstrate that accumulated atherosclerotic gangliosides promote platelet adhesion to collagen, the major component of the subendothelial matrix. Furthermore, this activity is mediated by an effect of the gangliosides on the collagen-binding integrin alpha2beta1. This activity may provide a mechanism for the development of platelet thrombi at sites where atherosclerotic gangliosides accumulate and help to explain the role of platelets in the process of atherosclerotic disease progression.
Aged↗
Gangliosides enhance migration of mouse B16-melanoma cells through artificial basement membrane alone or in presence of laminin or fibronectin.
The migration of B16LuF1 cells, B16-melanoma cells of lower metastatic potential to lung was enhanced through artificial basement membrane in presence of gangliosides of B16LuF1 cells as well as gangliosides of B16-melanoma cells of higher metastatic potential to lung, namely, B16LuF5 and B16LuF10 cells. The same concentration (50 microM) of gangliosides of B16LuF1, B16LuF5 and B16LuF10 cells gradually increased the migration of B16LuF1 cells through basement membrane. Moreover, B16LuF10 cell gangliosides modified the migratory effect of laminin and fibronectin on B16LuF1 cells. Laminin alone increased migration of B16LuF1 cells whereas fibronectin alone decreased migration of the same cells. When B16LuF10 cell gangliosides were used in combination with fibronectin, gangliosides removed the migration inhibitory effect of fibronectin resulting in net enhancing effect. Gangliosides in association with laminin also increased the enhancing effect of laminin on migration of B16LuF1 cells. Thus, gangliosides showed additive enhancing effect when used in combination with laminin. However, effect of individual gangliosides were different. Out of six gangliosides isolated from B16LuF10 cells only two gangliosides corresponding to standard gangliosides GM2 and GM3 enhanced migration of B16LuF1 cells. The migration of B16LuF1 cells in presence of each of the remaining four gangliosides corresponding to GT1b, GD1b, GD1a and GM1 was not altered and was comparable to that of untreated control. Thus, gangliosides of B16 melanoma cells alone or in combination with laminin or fibronectin enhanced migration of B16 melanoma cells through artificial basement membrane, suggesting possible role of tumor gangliosides during invasion of metastatic tumor cells through basement membrane of the surrounding tissues in vivo.
Animals↗
Neuroblastomas of infancy exhibit a characteristic ganglioside pattern.
BACKGROUND: Gangliosides are membrane-bound glycolipid molecules particularly prominent in neural tissue. Changes in ganglioside expression during embryologic development result from a shift in biosynthesis from the fetal b pathway to the adult a pathway. Tumor gangliosides may play a role in the clinical behavior of certain subtypes of neuroblastoma. Because neuroblastoma, which presents in infancy, has a different biologic and clinical phenotype than that which presents in older children, the authors determined whether differences in ganglioside biosynthesis exist between these two neuroblastoma subgroups. METHODS: Sixty-eight tumor specimens (25 diagnosed by screening and 43 diagnosed clinically) were obtained from the Quebec Neuroblastoma Screening Project. Gangliosides were isolated and purified by solvent partitioning, separated by high performance thin-layer chromatography, and quantitated by scanning densitometry. The sum of a and b pathway gangliosides were determined for each tumor. RESULTS: Gangliosides of the b (fetal) pathway predominated in both screened and clinically diagnosed tumors of patients younger than 1 year of age. Twenty-three of 25 screened patients (92%) and 21 of 23 patients with clinically diagnosed tumors at younger than 1 year of age (91%) had tumor b pathway ganglioside content greater than 60%. In contrast, tumors of only 8 of 20 patients 1 year or older (40%) had b pathway ganglioside predominance. Predominance of b pathway tumor gangliosides correlated with improved outcome. Event free survival was significantly higher among patients with b pathway ganglioside tumor content greater than 60% versus those with b pathway ganglioside tumor content less than 60% (118.1 +/- 3.9 months vs. 69.2 +/- 8.6 months, P < 0.01). CONCLUSIONS: Fetal patterns of ganglioside biosynthesis predominate in neuroblastoma tumors from patients younger than 1 year of age and adult patterns of ganglioside biosynthesis predominate in tumors from older children, supporting the view that neuroblastoma consists of distinct but overlapping disorders, and that gangliosides may play a biologic role in the clinical differences among these patients.
Chromatography, Thin Layer↗
Subcellular distribution and biosynthesis of rat liver gangliosides.
Gangliosides have generally been assumed to be localized primarily in the plasma membrane. Analysis of gangliosides from isolated subcellular membrane fractions of rat liver indicated that 76% of the total ganglioside sialic acid was present in the plasma membrane. Mitochondria and endoplasmic reticulum fractions, while containing only low levels of gangliosides on a protein basis, each contained approx. 10% of total ganglioside sialic acid. Gangliosides also were present in the Golgi apparatus and nuclear membrane fractions, and soluble gangliosides were in the supernatant. Individual gangliosides were non-homogeneously distributed and each membrane fraction was characterized by a unique ganglioside composition. Plasma membrane contained only 14 and 28% of the total GD1a and GD3, respectively, but 80-90% of the GM1, GD1b, GT1b and GQ1b. Endoplasmic reticulum, when corrected for plasma membrane contamination, contained only trace amounts of GM1, GD1b, GT1b and GQ1b, but 11 and 5% of the total GD1a and GD3, respectively. The ganglioside composition of highly purified endoplasmic reticulum was similar. Ganglioside biosynthetic enzymes were concentrated in the Golgi apparatus. However, low levels of these enzymes were present in the highly purified endoplasmic reticulum fractions. Pulse-chase experiments with [3H]galactose revealed that total gangliosides were labeled first in the Golgi apparatus, mitochondria and supernatant within 10 min. Labeled gangliosides were next observed at 30 min in the endoplasmic reticulum, plasma membrane and nuclear membrane fractions. Analysis of the individual gangliosides also revealed that GM3, GM1, GD1a and GD1b were labeled first in the Golgi apparatus at 10 min. These studies indicate that gangliosides synthesized in the Golgi apparatus may be transported not only to the plasma membrane, but to the endoplasmic reticulum and to other internal endomembranes as well.
Animals↗
Developmental profiles of gangliosides in trisomy 19 mice.
The ganglioside composition of the cerebrum, cerebellum, brainstem, liver, heart, and spleen was analyzed quantitatively in trisomy 19 (Ts19) mice aged 4 to 12 days postpartum. The developmental profiles of cerebral gangliosides were similar in Ts19 mice and control littermates: Total ganglioside-sialic acid as well as the proportions of the individual gangliosides GD1a and GM1 increased with age, while the percentages of GQ1b and GT1b decreased during development. Both the accretion of the total ganglioside content and the development of the individual ganglioside fractions were delayed by 2-3 days in the Ts19 telencephalon. Likewise, the shift from the b- to the a-pathway of ganglioside synthesis was retarded. Ganglioside development was equally delayed in the cerebellum and the brainstem of Ts19 mice. Since in Ts19 mice, morphogenesis of several brain regions is similarly delayed by 2 days, these results confirm the usefulness of gangliosides as biochemical markers for brain maturation. In contrast to brain gangliosides, the ganglioside composition of the Ts19 livers was clearly distinguished from that of control livers. Total ganglioside-bound sialic acid was increased by 35-50% in Ts19 livers. This elevation in ganglioside content not explicable by a simple delay in development was mainly due to an increase in GD3 and fraction 2, which is likely to contain GD1a and GD1b. In contrast, GM2 which increased considerably with age in control mice persisted on a low level in Ts19 livers. Comparable alterations of the ganglioside pattern were neither observed in the spleen nor in the heart of Ts19 mice. The data presented give additional evidence that ganglioside synthesis in the liver is under a different regulation mechanism than that in the brain, heart, and spleen.
Animals↗
Human and bovine milk: comparison of ganglioside composition and enterotoxin-inhibitory activity.
Milk gangliosides inhibit Vibrio cholerae enterotoxin and Escherichia coli heat-labile enterotoxin. Human milk gangliosides showed considerably higher enterotoxin-inhibitory activity compared to bovine and formula milk gangliosides as measured in vitro by enzyme-linked immunosorbent assay and in vivo in rabbit small bowel loops. While gangliosides from less than 1 ml human milk inhibited 0.1 microgram choleratoxin in vitro and in vivo, five to 10 times higher amounts of bovine milk gangliosides were necessary to achieve similar results. Analysis of the ganglioside composition in human, bovine, and bovine milk-based formula milk showed that the ganglioside patterns in human and bovine milk differed markedly. The ganglioside patterns of bovine milk and formula milk appeared identical. In human or bovine milk, the total amount of gangliosides was 11 mg/liter compared to 6 mg/liter in formula milk. The predominating ganglioside in human milk, monosialoganglioside 3 (74% of total gangliosides), was only a minor component (3%) of bovine milk gangliosides. Disialoganglioside 3 represented 80% of bovine milk gangliosides compared to 25% of the human milk gangliosides. Trace amounts of monosialoganglioside 1 were detected in human, as well as in bovine, milk by a sensitive high performance thin-layer chromatography immunoassay. The monosialoganglioside 1 content in human milk was 10 times higher than in bovine milk. We conclude that the higher nonimmunoglobulin enterotoxin-inhibitory activity in human milk compared to bovine milk is associated with the differences in the ganglioside fraction.
Animals↗