title: NEU3 sialidase is activated under hypoxia and protects skeletal muscle cells from apoptosis through the activation of the epidermal growth factor receptor signaling pathway and the hypoxia-inducible factor (HIF)-1α.
abstract: NEU3 sialidase, a key enzyme in ganglioside metabolism, is activated under hypoxic conditions in cultured skeletal muscle cells (C2C12). NEU3 up-regulation stimulates the EGF receptor signaling pathway, which in turn activates the hypoxia-inducible factor (HIF-1α), resulting in a final increase of cell survival and proliferation. In the same cells, stable overexpression of sialidase NEU3 significantly enhances cell resistance to hypoxia, whereas stable silencing of the enzyme renders cells more susceptible to apoptosis. These data support the working hypothesis of a physiological role played by NEU3 sialidase in protecting cells from hypoxic stress and may suggest new directions in the development of therapeutic strategies against ischemic diseases, particularly of the cerebro-cardiovascular system.
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, 20090 Segrate (Milan), Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scaringi
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.forename: Nadia
authors.initials: N
authors.lastname: Papini
authors.forename: Federica
authors.initials: F
authors.lastname: Cirillo
authors.forename: Erika
authors.initials: E
authors.lastname: Conforti
authors.forename: Sonia
authors.initials: S
authors.lastname: Bergante
authors.forename: Cristina
authors.initials: C
authors.lastname: Tringali
authors.forename: Andrea
authors.initials: A
authors.lastname: Garatti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
authors.forename: Bruno
authors.initials: B
authors.lastname: Venerando
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Menicanti
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D049109:Cell Proliferation; D019610:Cytoprotection; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D005679:G(M3) Ganglioside / Q000378:metabolism; D020868:Gene Silencing; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D032342:Muscle Cells / Q000166:cytology* / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology*; D009439:Neuraminidase / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D005679:G(M3) Ganglioside; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016329:Sp1 Transcription Factor; D013107:Sphingolipids; D051705:Sp3 Transcription Factor; D012799:Sialyltransferases; C021343:haematoside synthetase; D066246:ErbB Receptors; C511796:Neu3 protein, mouse; D009439:Neuraminidase; D020169:Caspases