Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats

Cohen-Forterre, Lisette; André, Jocelyne; Mozère, G; Peyroux, J.; Sternberg, M.

doi:10.1016/0006-2952(90)90549-z

Cited by 24 publications

(15 citation statements)

References 27 publications

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“…This concept does not conflict with our findings, although NEU3 cannot remove sialic acids from the receptor protein itself because of an inability to act on glycoproteins (4 -10). It has been observed that endogenous sialidase activity in the kidney (34) and retina (35) of diabetic rats is higher than in controls, with 4-methylumbelliferyl-neuraminic acid as the substrate. However, this is not likely to be directly connected to the present results, because the substrate is targeted by lysosomal type sialidase, which could account for the observed activity.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Plasma Membrane-associated Sialidase Attenuates Insulin Signaling in Transgenic Mice

Sasaki

Hata

Suzuki

et al. 2003

Journal of Biological Chemistry

108

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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 ␤-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.Gangliosides are a family of sialic acid-containing glycosphingolipids present in the cell surface membranes. Several lines of evidence suggest their important functional roles in regulating a wide range of biological processes including cell growth, cell differentiation, and transmembrane signaling (1-3). Most of the observations on ganglioside function, however, have been performed so far by using bacterial sialidases and exogenous gangliosides to mimic in vivo expression. To obtain further insights into their physiological significance and regulation mechanism, it is necessary to focus on endogenous sialidases responsible for ganglioside hydrolysis inside the cells. Three types of mammalian sialidase have been cloned and established to have low identity with each other in their primary structure. They differ in enzymatic properties and subcellular localization, being mainly found in lysosomes (Neu1), cytosol (Neu2), and plasma membranes (Neu3). Other than the contribution of lysosomal sialidase to glycoconjugate catabolism in lysosomes, their cellular roles are not well understood. The fact that plasma membrane sialidase is unique in specifically hydrolyzing gangliosides (4 -10) and in its subcellular localization in plasma membranes, where levels of other glycosidases are very low, suggests participation in cell surface events through modulation of gangliosides. To obtain evidence of this, we previously cloned sialidase cDNAs of mammalian origin (8, 9, 11, 12), and we have recently investigated effects of overexpression in transgenic...

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Section: Discussionmentioning

confidence: 99%

Overexpression of Plasma Membrane-associated Sialidase Attenuates Insulin Signaling in Transgenic Mice

Sasaki

Hata

Suzuki

et al. 2003

Journal of Biological Chemistry

108

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“…Although several lines of evidence suggest that insulin resistance and diabetes mellitus may lead to changes in the glycome, very little is known about this (15,16). For example, it was shown that alterations in the activity of the enzymes involved in glycosylation result in changes in the sialic acid (Sia) and Fuc content in insulin-resistant patients and animals (17)(18)(19). Insulin deficiency can lead to an increase in the plasma concentration of Sia (19).…”

Section: Discussionmentioning

confidence: 99%

N-Glycosylation Pattern of Human Placental Insulin-Like Growth Factor and Insulin Receptors in Well-Controlled Pregestational Diabetes Mellitus

Robajac¹,

Masnikosa²,

Filimonović³

et al. 2012

Journal of Medical Biochemistry

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Summary: Diabetes mellitus is a complex disease that leads to alterations in the glycosylation of proteins. Insulin-like growth factor and insulin receptors are involved in the regulation of fetal and placental growth and development. In this work the N-glycans of these receptors, originating from placentas obtained from pregnancies complicated by pregestational insulin dependent diabetes mellitus, were studied. Dia betic mothers were under regular insulin therapy. Solubilised membrane samples from healthy and diabetic placentas were analysed using lectin-affinity chromatography. N-glycans bound to insulin-like growth factor and insulin receptors were studied in terms of their interaction with eleven aga rose--immobilised lectins: wheat germ agglutinin, succinyla ted wheat germ agglutinin, Ricinus communis agglutinin I, Sambucus nigra agglutinin, Erythrina cristagalli lectin, Ulex europaeus agglutinin, Lens culinaris agglutinin, Canavalia en siformis lectin, Phaseolus vulgaris erythro-and leukoagglutinin and Maackia amurensis agglutinin. A very similar type of N-glycans and content of the terminal saccharide residues were found in both groups of placentas. The results of this work suggest that the tight glycemic control may prevent alterations in the glycosylation of insulin-like growth factor and insulin receptors, thus maintaining physiological homeostasis during pregnancy and fetal growth.Keywords: diabetes mellitus, insulin-like growth factor receptors, insulin receptor, N-glycosylation, placenta Kratak sadr`aj: Dijabetes melitus je kompleksno oboljenje koje uzrokuje promene u na~inu glikozilovanja prote ina. Receptori za insulin i insulinu sli~ne faktore rasta u~es -tvuju u regulaciji rasta i razvitka fetusa i placente. U ovom radu ispitivani su N-glikani vezani kovalentnom vezom za pome nute receptore. Receptori za insulin i insulinu sli~ne faktore rasta dobijeni su iz placenti majki sa pregestacijskim insu lin-zavisnim dijabetesom. Dijabeti~ne majke bile su na re dov noj terapiji insulinom. Uzorci }elijskih membrana, izolovani i solubilizovani iz placenti zdravih majki i majki sa dijabetesom, analizirani su primenom lektinske afinitetne hromatografije. Ispitivana je interakcija N-glikana vezanih za receptore sa jedanaest razli~itih lektina, imobilisanih na agaroznom gelu: lektin iz p{eni~nih klica, sukcinilovani lektin iz p{eni~nih klica, Ricinus communis lektin I, lektin iz kore zove, lektin iz koralnog drveta, lektin iz Ulex europaeus-a, lektin iz so~iva, konkanavalin A, dva lektina iz pasulja i lektin iz Maackia amurensis-a. Rezultati ovog rada pokazali su da receptori za insulin i insulinu sli~ne faktore rasta poreklom iz humane placente zdravih majki i onih sa pregestacijskim dijabetesom imaju veoma sli~an tip N-glikana kao i sastav terminalnih ostataka saharida, {to ukazuje na to da se dobrom kontrolom glikemije kod trudnica sa dijabetesom mogu spre~iti promene u na~inu gliko zilova nja ovih receptora, ~ime bi se pomoglo odr`avanju fiziolo{ke homeostaze za vreme rasta fetusa.

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“…Assays were carried out as previously described [6]. Briefly, 80-pl aliquots containing about 0.2 mg protein of the en zyme preparation were incubated at 30 °C for 30 min with 20 pi of the 0.2 M Tris-HCl pH 6.5 buffer con taining 0.1 jWMnCh and 0.1 % Triton X-100, 10 pi of asialofetuin (50 mg/ml.…”

Section: Animals and Experimental Proceduresmentioning

confidence: 99%

“…For sialyltransferase activity determination, the left kidney was ho mogenized in 0.1 MTris-HCl buffer, pH 6.8, contain ing 0.1 % T riton X-100 and 2 mM ß-mercaptoethanol (4 ml/g kidney); the homogenate was subjected to 7 brief ultrasonic series at an amplitude of 2 emitted from a Branson Sonifier (B 15) and then centrifuged for 25 min at 10,000 g; the supernatant was used as enzyme source. [6], Protein concentrations were measured by the meth od of Lowry et al [9], Aliquots of homogenates were solubilized first in 0.1 TVNaOH at 37 °C for 2 h.…”

Section: Preparation Of Kidney Tissue Fractionsmentioning

confidence: 99%

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Sex and Age Dependence of Rat Kidney Sialidase

Cohen-Forterre¹,

André²,

Sternberg³

1992

Enzyme

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Rat kidney sialidase levels have been reported to be markedly altered in pathological states such as diabetes. This was associated with a modification of sialic acid levels. Therefore, it was interesting to study the variations of kidney sialidase and sialyltransferase activities and sialic acid content according to sex and age. This was carried out from birth to 210 days of age. The substrates used were sialyla(2-3)[^3H]-lactitol for sialidase activity, asialofetuin and [^14C]-CMPNeu5Ac for sialyltransferase activity. In males sialidase activity increased until 32 days then slightly declined. In females, the activity increased and leveled off at 135 days of age. Higher sialidase activity was observed in females than in males from 56 days of age. Gonadectomy had no effect on this activity. In both sexes, sialyltransferase activity decreased markedly with age. This activity was higher in females than in males, whereas sialic acid levels varied only moderately with age and were slightly higher in females.

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Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats

Cited by 24 publications

References 27 publications

Overexpression of Plasma Membrane-associated Sialidase Attenuates Insulin Signaling in Transgenic Mice

Overexpression of Plasma Membrane-associated Sialidase Attenuates Insulin Signaling in Transgenic Mice

N-Glycosylation Pattern of Human Placental Insulin-Like Growth Factor and Insulin Receptors in Well-Controlled Pregestational Diabetes Mellitus

Sex and Age Dependence of Rat Kidney Sialidase

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