Glycobiology Advance Access published online on March 27, 2007
Glycobiology, doi:10.1093/glycob/cwm034
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Trypanosome trans-sialidase mediates neuroprotection against oxidative stress, serum/glucose deprivation and hypoxia-induced neurite retraction in Trk-expressing PC12 cells
2 Department of Microbiology & Immunology, Queen's University, Kingston, Ontario, K7L3N6, Canada
3 Fundamental and Applied Molecular Biology, Ghent University, Flanders Interuniversity Institute for Biotechnology (V.I.B.) Technologiepark 927 B-9052 Gent-Zwijnaarde Belgium
4 Laboratory of Neural Signaling, Cell Biology Group, Robarts Research Institute, London, Ontario, N6A 5K8, Canada
1 To whom correspondence should be addressed; Tel.: +1-613-533-2457; Fax: +1-613-533-6796; e-mail: szewczuk{at}post.queensu.ca
Received on October 26, 2006; revised on February 20, 2007; accepted on March 16, 2007
Trypanosome trans-sialidase (TS) is a sialic acid-transferring enzyme and a novel ligand of TrkA receptors but not of neurotrophin receptor p75NTR. Here we show that TS targets TrkB receptors on TrkB-expressing pheochromocytoma PC12 cells and colocalizes with TrkB receptor internalization and phosphorylation (pTrkB). Wild type TS but not the catalytically inactive mutant TS
Asp98-Glu induces pTrkB and mediates cell survival responses against death caused by oxidative stress in TrkA- and TrkB-expressing cells like those seen with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). These same effects are not observed in Trk deficient PC12nnr5 cells, but are re-established in PC12nnr5 cells stably transfected with TrkA or TrkB, are partially blocked by inhibitors of tyrosine kinase (K-252a), MAP/MEK protein kinase (PD98059) and completely blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI-3K). Both TrkA- and TrkB-expressing cells pretreated with TS or their natural ligands are protected against cell death caused by serum/glucose deprivation or from hypoxia-induced neurite retraction. The cell survival effects of NGF and BDNF against oxidative stress are significantly inhibited by the neuraminidase inhibitor, Tamiflu. Together these observations suggest that trypanosome trans-sialidase mimics neurotrophic factors in cell survival responses against oxidative stress, hypoxia-induced neurite retraction and serum/glucose deprivation. In addition, the cell survival responses mediated by NGF and BDNF in Trk-expressing cells may be dependent on cellular sialidase(s) activation.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Weinkauf and M. PereiraPerrin Trypanosoma cruzi Promotes Neuronal and Glial Cell Survival through the Neurotrophic Receptor TrkC Infect. Immun., April 1, 2009; 77(4): 1368 - 1375. [Abstract] [Full Text] [PDF]
|
|