Trypanosome trans-sialidase mediates neuroprotection against oxidative stress, serum/glucose deprivation, and hypoxia-induced neurite retraction in Trk-expressing PC12 cells

Trypanosome trans-sialidase (TS) is a sialic acid-transferring enzyme and a novel ligand of tyrosine kinase (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 interna...

Full description

Saved in:
Bibliographic Details
Published in:Glycobiology (Oxford) 2007-07, Vol.17 (7), p.725-734
Main Authors: Woronowicz, Alicja, Amith, Schammim Ray, Davis, Vanessa W, Jayanth, Preethi, De Vusser, Kristof, Laroy, Wouter, Contreras, Roland, Meakin, Susan O, Szewczuk, Myron R
Format: Article
Language:English
Subjects:
Animals
Cell Survival
Enzyme Inhibitors - pharmacology
Glial Cell Line-Derived Neurotrophic Factor - metabolism
Glucose - metabolism
Glycoproteins - metabolism
Hypoxia
Nerve Growth Factor - metabolism
Neuraminidase - metabolism
Oseltamivir - pharmacology
Oxidative Stress
PC12 Cells
Rats
Receptor, trkB - metabolism
Serum - metabolism
Trypanosoma
Trypanosoma cruzi - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Trypanosome trans-sialidase (TS) is a sialic acid-transferring enzyme and a novel ligand of tyrosine kinase (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 TSΔAsp98-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), mitogen-activated protein/mitogen-activated kinase (PD98059) and completely blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). 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 TS mimics neurotrophic factors in cell survival responses against oxidative stress, hypoxia-induced neurite retraction and serum/glucose deprivation.
ISSN:0959-6658
1460-2423
DOI:10.1093/glycob/cwm034