Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.53 (sialidase)
2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney cortex sialic acid level, sialidase and sialyltransferase activities have been measured in spontaneously diabetic BB rats and in streptozotocin-diabetic rats (STZ). In untreated diabetic BB rats, at the onset of the disease, sialidase specific activity was found to be increased by 21% when compared with diabetes-resistant BB controls (P less than 0.05) whereas sialyltransferase activity was not significantly modified and bound sialic acid concentration was diminished (P less than 0.05). In diabetic BB rats submitted to a minimal insulin therapy, during 3 months of disease, sialidase activity and sialic acid concentration were similar to those of Wistar age-matched controls. In STZ-diabetic Wistar rats, sialidase specific activity was increased by 76% after 5 months of disease when compared to age-matched Wistar controls (P less than 0.01); in contrast, specific sialyltransferase activity was decreased by 21% (P less than 0.05); these enzymatic alterations were associated with a decrease in bound sialic acid concentration (P less than 0.01); 1 month's insulin therapy, started 4 months after onset of the disease, normalized sialidase activity but had no effect on sialyltransferase activity and sialic acid concentration; treatment with sorbinil prevented cataract development but had no effect on sialidase activity whereas it emphasized the decrease in sialyltransferase activity and sialic acid concentration. The disturbances in the enzyme activities concerned with sialoglycoconjugate metabolism observed in experimental and spontaneous diabetes may be responsible for the decreased bound sialic acid content observed in the rat kidney cortex.
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PMID:Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats. Influence of insulin and sorbinil treatments. 220 Apr 8

The level of sialic acid in the diabetic polymorphonuclear leucocytes was found to be significantly reduced as compared to normal. More pronounced effects were observed with ketoacidotic as compared to nonketoacidotic diabetic polymorphonuclear leucocytes. Activity of sialic acid degrading enzyme, sialidase, was found to be increased with more pronounced effect in the ketotic state. Diabetic patients treated either with intravenous insulin or oral hypoglycemic drugs showed restoration to normalcy in both sialic acid content and sialidase activity. The implications of the result are discussed.
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PMID:Sialic acid content and sialidase activity of polymorphonuclear leucocytes in diabetes mellitus. 646 86

The ability of pertussis toxin (PT) to recognize and bind to surface proteins on cells derived from pancreatic insulin-secreting beta cells and alpha cell-like glucagon-producing cells was investigated employing HIT-T15 (beta cell-derived) and In-R1-G9 (alpha cell-like) cell lines. PT recognition of membrane binding proteins on HIT-T15 and In-R1-G9 cells was first assessed with immunofluorescence microscopy in tissue culture. Both cell lines were equally well recognized by PT. N-octylglucoside extracts of whole cells and isolated membranes were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and blotted onto nitrocellulose membranes. PT, the B-oligomer, or the isolated PT dimers S2-S4 and S3-S4 recognized distinct proteins in HIT-T15 and In-R1-G9 cells of about 220 kDa. Recognition by the sialic acid specific Sambucus nigrica lectin identified these proteins as sialoglycoproteins. Incubation of the blotted membrane proteins with sialidase or pretreatment of PT with anti-PT polyclonal antibodies abolished the recognition and binding of these proteins by PT. To demonstrate that these glycoproteins are also able to transduce PT mediated effects and thus might serve as PT binding proteins, the stimulation of insulin secretion in HIT-T15 cells was assessed. As the secretion of insulin in HIT-T15 cells increased about 30% upon interaction with PT it was concluded that these glycoproteins are indeed functional as PT receptors.
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PMID:Identification of binding proteins for pertussis toxin on pancreatic beta cell-derived insulin-secreting cells. 756 12

Leucocyte surface sialic acid content influences surface charge, deformability, and leucocyte-endothelial interaction. Abnormal leucocyte structure and function contributes both to microvascular damage and diabetic complications. The aim of this study was to investigate altered leucocyte SA metabolism in diabetic subjects and measure lysosomal sialidase which regulates leucocyte surface sialylation. We examined 26 Type 1 (insulin-dependent) diabetic subjects with retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched normal control subjects. Sialidase was assayed in freshly prepared sonicates of pure mononuclear leucocytes (MNLs), using the fluorometric substrate 4-methyl-umbelliferyl-N-acetylneuraminic acid. In the subjects with diabetes there was a significant negative correlation between MNL sialidase activity and both HbA1c (rs = 0.37, p = 0.007) and fructosamine (rs = -0.31, p = 0.026). MNL sialidase activity was significantly decreased in diabetic subjects with clinical evidence of complications compared to control subjects. HbA1c was significantly higher (p = 0.036) in diabetic patients with complications compared to those without. The observed decrease in MNL sialidase activity related to diabetic control may be important in the pathogenesis of vascular damage. Diabetes-associated changes in sialylation of functional cell surface glycoconjugates may have important clinical consequences.
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PMID:Decreased sialidase activity in mononuclear leucocytes of type 1 diabetic subjects: relationship to diabetic complications and glycaemic control. 758 4

The folk admonition to starve a fever may have a scientific basis. Fevers due to infectious organisms that produce neuraminidase (sialidase) may contribute to the pathophysiology of autoimmune conditions. Neuraminidase unmasks host cellular lectins that interact with food lectins and can induce human leukocyte antigen type II (HLA II) expression. HLA II can then bind food lectins and serve as targets for antibody production. Some of these antibodies can then cross-react and attack healthy tissue, inducing disease. The example of insulin-dependent diabetes mellitus is discussed, helping to explain why infectious organisms and dairy product ingestion appear to be linked to some cases of this disease. Genetic variants and other factors may contribute to disease pathogenesis, so this model does not explain all instances of autoimmune disease. Fasting as a way to avoid the process by not introducing food lectins is briefly reviewed. Neuraminidase inhibitors might be useful in preventing genesis of autoimmunity during infection, although this possibility has not been formally tested.
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PMID:Proposed biomolecular theory of fasting during fevers due to infection. 1170 68

Plasma membrane-associated sialidase is a key enzyme for ganglioside hydrolysis, thereby playing crucial roles in regulation of cell surface functions. Here we demonstrate that mice overexpressing the human ortholog (NEU3) develop diabetic phenotype by 18-22 weeks associated with hyperinsulinemia, islet hyperplasia, and increased beta-cell mass. As compared with the wild type, insulin-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate I was significantly reduced, and activities of phosphatidylinositol 3-kinase and glycogen synthase were low in transgenic muscle. IR phosphorylation was already attenuated in the younger mice before manifestation of hyperglycemia. Transient transfection of NEU3 into 3T3-L1 adipocytes and L6 myocytes caused a significant decrease in IR signaling. In response to insulin, NEU3 was found to undergo tyrosine phosphorylation and subsequent association with the Grb2 protein, thus being activated and causing negative regulation of insulin signaling. In fact, accumulation of GM1 and GM2, the possible sialidase products in transgenic tissues, caused inhibition of IR phosphorylation in vitro, and blocking of association with Grb2 resulted in reversion of impaired insulin signaling in L6 cells. The data indicate that NEU3 indeed participates in the control of insulin signaling, probably via modulation of gangliosides and interaction with Grb2, and that the mice can serve as a valuable model for human insulin-resistant diabetes.
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PMID:Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice. 1273 Feb 4

Membrane microdomains rich in gangliosides are recognized as being critical for proper compartmentalization of insulin signaling. Plasma membrane-associated sialidase, NEU3, is a key enzyme for ganglioside hydrolysis. We previously reported that mice overexpressing NEU3 mainly in muscles developed severe insulin-resistant diabetes. To examine the possible contributions of NEU3 to in vivo insulin sensitivity and glucose tolerance, NEU3 was expressed by using adenoviral vectors in the livers of C57BL/6 mice on standard and high-fat diets, and insulin-resistant KKAy mice on standard diets. Hepatic NEU3 overexpression paradoxically improved glucose tolerance and insulin sensitivity in the C57BL/6 mice fed standard diets, and glucose tolerance in the C57BL/6 mice fed high-fat diets and in KKAy mice. Hepatic NEU3 overexpression increased hepatic glycogen deposition and triglyceride accumulation, and enhanced the hepatic peroxisome proliferator-activated receptor gamma and fetuin expression in the C57BL/6 mice on standard and high-fat diets, and in KKAy mice. Thin-layer chromatographic analysis demonstrated increased levels of GM1 and markedly reduced GM3 in the livers of mice with hepatic NEU3 overexpression (NEU3 mice). Basal and insulin-stimulated tyrosine phosphorylations of insulin receptor substrate 1 were significantly increased, but tyrosine phosphorylations of the insulin receptor and insulin receptor substrate 2 in the NEU3 liver were unchanged. Insulin-stimulated tyrosine phosphorylations of the insulin receptor were increased in adipose tissues of NEU3 mice. These results suggest that hepatic NEU3 overexpression improves insulin sensitivity and glucose tolerance through modification of ganglioside composition and peroxisome proliferator-activated receptor gamma signaling. Our findings also provide further evidence that NEU3 is an important regulator of insulin sensitivity and glucose tolerance.
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PMID:Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice. 1729 33

Mammalian sialidases, glycosidases responsible for the removal of sialic acids from glycoproteins and glycolipids, has been implicated to participate in many biological processes as well as in lysosomal catabolism. Among those forms identified to date, plasma membrane-associated sialidase, Neu3, is a key enzyme in degradation of gangliosides, for which it exhibits a special substrate preference. This sialidase has been shown to control transmembrane signalling for many cellular processes, including cell differentiation, cell growth and apoptosis, and human orthologue NEU3 is markedly up-regulated in various cancers. It is known to suppress apoptosis in cancer cells. Furthermore, its overexpression causes impaired glucose tolerance and hyper-insulinaemia together with overproduction of insulin in enlarged islets in the transgenic mice. The present review primarily summarizes our recent results, focusing on Neu3 as a regulator of transmembrane signalling.
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PMID:Plasma membrane-associated sialidase as a crucial regulator of transmembrane signalling. 1863 3

The klotho gene encodes a single-pass transmembrane protein that forms a complex with multiple fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for FGF23, a bone-derived hormone that induces negative phosphate balance. Defects in either Klotho or Fgf23 gene expression cause not only phosphate retention but also a premature-aging syndrome in mice, unveiling a potential link between phosphate metabolism and aging. In addition, the extracellular domain of Klotho protein is clipped on the cell surface and secreted into blood stream, potentially functioning as an endocrine factor. The secreted Klotho protein has a putative sialidase activity that modifies glycans on the cell surface, which may explain the ability of secreted Klotho protein to regulate activity of multiple ion channels and growth factors including insulin, IGF-1, and Wnt. Secreted Klotho protein also protects cells and tissues from oxidative stress through a mechanism yet to be identified. Thus, the transmembrane and secreted forms of Klotho protein have distinct functions, which may collectively affect aging processes in mammals.
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PMID:Klotho and aging. 1923 Aug 44

Two degradative activities were found in a recombinant Chinese hamster ovary cell culture. These activities became more dominant under high cell density and extended running time, as achieved in a semi-continous perfusion culture. The first, insulin degradative activity caused a growth upset in the 3rd cycle of the perfusion culture and shortened the length of the bioreactor process. The second activity, derived from the neutral pH stable sialidase, was found to affect the integrity of the carbohydrate structure of the recombinant protein, causing increase in heterogeneity in molecular weight and pI of the glycoforms. The most efficient way to overcome these problems may be the use of genetically altered 'designer cells' as the production cell line.
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PMID:Degradative activities in a recombinant chinese hamster ovary cell culture. 2235 14


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