Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma of normal human individuals was shown to contain an inhibitor of Trypanosoma cruzi neuraminidase (NAase; acylneuraminyl hydrolase, sialidase, EC 3.2.1.18). The inhibitor has been purified to homogeneity by PEG precipitation, CM Affi-Gel Blue Sepharose chromatography, and gel filtration. The purified preparation inhibits T. cruzi NAase at a concentration as low as 10(-9) M and has no effect at concentrations at least 100 times higher on any of the other NAases tested, including those from influenza virus, the closely related trypanosome Trypanosoma rangeli, and mammalian NAases. The inhibitor is unique in that it prevents T. cruzi desialylation of intact mammalian cells but does not prevent desialylation of soluble glycoconjugates. In addition, the isolated material is effective in inhibiting the T. cruzi NAase whether the enzyme is on the parasite outer membrane or in solution. Molecular characterization indicates that the inhibitor is a glycoprotein with a Mr of 246,000 +/- 20,000 composed of subunits of Mr 28,000 +/- 2000. Its plasma concentration is at least 60 micrograms/ml. The mechanism of action has not been fully elucidated, but it appears to be noncompetitive. Attempts to match the isolated NAase inhibitor with known plasma glycoproteins have not been successful. In view of this and of the specificity of the inhibitor for T. cruzi, we have named the inhibitor "cruzin." This finding suggests a different approach in investigating the role that NAase plays in host-parasite interaction.
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PMID:Specific inhibition of Trypanosoma cruzi neuraminidase by the human plasma glycoprotein "cruzin". 355 30

Erythropoiesis-stimulating agents (ESAs) are widely used for treating chronic kidney disease (CKD)-associated anemia. The biological activity of ESAs is mainly regulated by the number of sialic acid-containing carbohydrates on the erythropoietin (EPO) peptide. Sialidase, a sialic acid-metabolizing enzyme that accumulates in CKD patients, is suspected of contributing to shortening the circulation half-life of ESAs. Epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.), is an EPO integrated with methoxypolyethylene glycol (PEG). It has been suggested that C.E.R.A. may exert a favorable therapeutic effect, even under conditions of elevated sialidase; however, no detailed investigation of the pharmacological profile of C.E.R.A. in the presence of sialidase has been reported. In the present study, we injected C.E.R.A. or EPO pre-incubated with sialidase into rats, and assessed the hematopoietic effect by reticulocyte count. The hematopoietic effect of C.E.R.A., but not EPO, was preserved after sialidase treatment, despite the removal of sialic acid. Proliferation of EPO-dependent leukemia cells (AS-E2) was significantly increased by desialylated C.E.R.A. and EPO compared to non-treated C.E.R.A. or EPO. In conclusion, we show that C.E.R.A. exerts a favorable hematopoietic effect even under conditions of elevated sialidase. Our findings may contribute to a better understanding of CKD and more effective therapeutic approaches based on a patient's profile of anemia.
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PMID:Epoetin beta pegol, but not recombinant erythropoietin, retains its hematopoietic effect in vivo in the presence of the sialic acid-metabolizing enzyme sialidase. 2708 58