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

Raffaella Scaringi, Marco Piccoli, Nadia Papini, Federica Cirillo, Erika Conforti, Sonia Bergante, Cristina Tringali, Andrea Garatti, Cecilia Gelfi, Bruno Venerando, Lorenzo Menicanti, Guido Tettamanti, Luigi Anastasia

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3153-3162
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number5
DOIs
Publication statusPublished - Feb 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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