| First Author | Rossi S | Year | 2009 |
| Journal | Biochim Biophys Acta | Volume | 1790 |
| Issue | 8 | Pages | 817-28 |
| PubMed ID | 19371771 | Mgi Jnum | J:153485 |
| Mgi Id | MGI:4365524 | Doi | 10.1016/j.bbagen.2009.04.006 |
| Citation | Rossi S, et al. (2009) The cytosolic sialidase Neu2 is degraded by autophagy during myoblast atrophy. Biochim Biophys Acta 1790(8):817-28 |
| abstractText | BACKGROUND: The sialidase Neu2 is a cytosolic enzyme which is fully expressed in mature muscle myofibers. METHODS: To investigate Neu2 expression during muscle atrophy, we employed an in vitro model consisting of terminally differentiated C2C12 myotubes exposed to different pro-atrophic stimuli that triggered catabolic pathways involved in proteasome activation or autophagy. RESULTS: Neu2 expression was unchanged in myotubes treated with TNF-alpha, a cytokine known to activate the proteasome. However, Neu2 transcript levels and enzymatic activity were downregulated in starved or dexamethasone-treated myotubes that showed proteosomal activation and several hallmarks of macroautophagy, such as formation of autophagosomes, the accumulation of LC3 dots and bulk degradation of long-lived proteins. Neu2 activity and protein levels were rescued upon cotreatment with the lysosomotropic agent NH4Cl, the autophagy inhibitor 3-methyladenine or cathepsin inhibitors, as well as by insulin administration, but were unaffected upon pharmacological inhibition of the proteasome. Moreover, HA- or GST-Neu2 recombinant fusion proteins were rapidly degraded in vitro by purified cathepsin L and B. Overall, we may conclude that Neu2 is degraded by lysosomal enzymes in myotubes undergoing autophagy-mediated atrophy. GENERAL SIGNIFICANCE: This study demonstrates that Neu2 enzyme degradation occurs in atrophic myotubes via macroautophagy and independently of proteasome activation. |
