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)

The neuraminidase/trans-sialidase of Trypanosoma cruzi, the agent of Chagas' disease, promotes differentiation and survival of growth factor-deprived neuronal and glial cells. To gain further insights into the possible neuroprotection of this parasite-derived counterpart of neurotrophic factors (PDNF), we sought to determine whether it mimics growth factors in a cellular model of neurodegenerative diseases. Ascertaining cell viability by morphology, vital dye exclusion, mitochondrial reducing function, and absence of DNA fragmentation, we show here that PDNF rescues from death two dopaminergic neuronal cell lines and one differentiated immortalized mesencephalic neurons exposed to the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP+), both widely used in models of Parkinson's disease. We further show that PDNF promoted survival at concentrations comparable to bona fide growth factors in a MAPK/Erk activation-dependent manner. PDNF also strongly suppresses the overproduction of MPTP-induced reactive oxygen species (ROS), and the activation of both initiator caspase-9 and effector caspase-3. This down-regulation of ROS and caspases explains, at least in part, the PDNF-induced salvaging of the dopaminergic cells from the Parkinsonism-promoting toxin, confirming the novel and striking functional mimicry by the trypanosome neuraminidase of host growth factors in a cellular model of neurodegeneration.
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PMID:PDNF, a human parasite-derived mimic of neurotrophic factors, prevents caspase activation, free radical formation, and death of dopaminergic cells exposed to the Parkinsonism-inducing neurotoxin MPP+. 1459 29

Human plasma membrane-associated sialidase (NEU3), specifically hydrolyzing gangliosides, plays crucial roles in the regulation of cell surface functions. Here we demonstrate that NEU3 mRNA level are increased in renal cell carcinomas (RCCs) compared with adjacent non-tumor tissues, significantly correlating with elevation of interleukin-6 (IL-6), a pleiotropic cytokine that has been implicated in immune responses and pathogenesis of several cancers, including RCCs. In human RCC ACHN cells, IL-6 treatment enhanced NEU3 promoter luciferase activity 2.5-fold and the endogenous sialidase activity significantly. NEU3 transfection or IL-6 treatment resulted in both suppression of apoptosis and promotion of cell motility, and the combination had synergistic effects. NEU3 scarcely affected MAPK- or IL-6-induced STAT3 activation but promoted the phosphatidylinositol 3-kinase (PI3K)/Akt cascade in both IL-6-dependent and -independent ways. Consistent with these data, NEU3 markedly inhibited staurosporine-induced caspase-3 activity and enhanced IL-6-dependent inhibition, which was abolished by LY294002, a PI3K inhibitor. Furthermore, IL-6 promoted Rho activation, and the effect was potentiated by NEU3, leading to increased cell motility that was again affected by LY294002. NEU3 silencing by siRNA resulted in the opposite: decreased Akt phosphorylation and inhibition of Rho activation. Glycolipid analysis showed a decrease in ganglioside GM3 and increase in lactosylceramide after NEU3 transfection, with these lipids apparently affecting cell apoptosis and motility. The results indicate that NEU3 activated by IL-6 exerts IL-6-mediated signaling, largely via the PI3K/Akt cascade, in a positive feedback manner and contributes to expression of a malignant phenotype in RCCs. NEU3 thus may be a useful target for RCC diagnosis and therapy.
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PMID:Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes interleukin-6-induced apoptosis suppression and cell motility. 1642 83

An escape mutant of human parainfluenza virus type 1 (hPIV1), which was selected by serial passage in the presence of a sialidase inhibitor, 4-O-thiocarbamoylmethyl-2-deoxy-2,3-didehydro-N-acetylneur-aminic acid (TCM-Neu5Ac2en), exhibited remarkable syncytium formation and virus-induced cell death in LLC-MK2 cells but no difference in susceptibility for the sialidase inhibitor TCM-Neu5Ac2en from that of wild-type hPIV1 strain C35 (WT). The mutant virus also had higher replication and plaque formation abilities. The mutant virus acquired two amino acid mutations, Glu to Gly at position 170 and Ala to Glu 442 in fusion (F) glycoprotein, but no mutations in haemaggulutinin-neuraminidase (HN) glycoprotein. Using cells co-expressing F and HN genes with site-specific mutagenesis, we demonstrated that a point mutation of Glu to Gly at position 170, which was estimated to be located in hPIV1 F glycoprotein heptad repeat 1, was required for obvious syncytium formation and caspase-3-dependent cell death. In contrast, wild-type F glycoprotein induced no synctium formation or cell death. The findings suggest that a single amino acid mutation of hPIV1 F glycoprotein promotes syncytium formation that is followed by caspase-3-dependent cell death.
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PMID:A single amino acid mutation at position 170 of human parainfluenza virus type 1 fusion glycoprotein induces obvious syncytium formation and caspase-3-dependent cell death. 2118 50

Apoptotic cells and subcellular microparticles expose increased sialidase activity on their surfaces, which results from caspase-3 dependent activation of plasma membrane associated Neuraminidase-1 (Neu1). Desialylation of dying cells is also known to promote efferocytosis. The intriguing question remained whether sialidase on the surface of dying cell merely acts on self targets (cis-action), or whether it can also cleave glycoepitopes of neighboring cells (trans-action). Here, we co-incubated human viable and apoptotic Jurkat lymphocytes or neutrophils with human erythrocytes and evaluated their glycoprofile for terminal sialic acids by agglutination assay, flow cytometry, ELISA and dot-blot analyses. Data suggest that erythrocytes were desialylated as soon as 3 hours after co-incubation with apoptotic cells, but not with viable ones. After co-incubation of L929 murine fibroblasts with viable or apoptotic murine L1210 cells the L929 cells gained a desialylated glycoprofile, only after co-incubation with apoptotic cells. Our data suggests that activated sialidase(s) on the surfaces of apoptotic cells are capable to desialylate neighboring cells in trans.
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PMID:Sweet kiss of dying cell: sialidase activity on apoptotic cell is able to act toward its neighbors. 2292 16

Benzene-induced erythropoietic depression has been proposed to be due to the production of toxic metabolites. Presently, the cytotoxicities of benzene metabolites, including phenol, catechol, hydroquinone, and 1,2,4-benzenetriol, to erythroid progenitor-like K562 cells were investigated. After exposure to these metabolites, K562 cells showed significant inhibition of viability and apoptotic characteristics. Each metabolite caused a significant increase in activities of caspase-3, -8, and -9, and pretreatment with caspase-3, -8, and -9 inhibitors significantly inhibited benzene metabolites-induced phosphatidylserine exposure. These metabolites also elevated expression of Fas and FasL on the cell surface. After exposure to benzene metabolites, K562 cells showed an increase in reactive oxygen species level, and pretreatment with N-acetyl-l-cysteine significantly protected against the cytotoxicity of each metabolite. Interestingly, the control K562 cells and the phenol-exposed cells aggregated together, but the cells exposed to other metabolites were scattered. Further analysis showed that hydroquione, catechol, and 1,2,4-benzenetriol induced a decrease in the cell surface sialic acid levels and an increase in the cell surface sialidase activity, but phenol did not cause any changes in sialic acid levels and sialidase activity. Consistently, an increase in expression level of sialidase Neu3 mRNA and a decrease in mRNA level of sialyltransferase ST3GAL3 gene were detected in hydroquione-, catechol-, or 1,2,4-benzenetriol-treated cells, but no change in mRNA levels of two genes were found in phenol-treated cells. In conclusion, these benzene metabolites could induce apoptosis of K562 cells mainly through caspase-8-dependent pathway and ROS production, and sialic acid metabolism might play a role in the apoptotic process.
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PMID:Phenolic metabolites of benzene induced caspase-dependent cytotoxicities to K562 cells accompanied with decrease in cell surface sialic acids. 2377 99