PMID- 17389653 OWN - NLM STAT- MEDLINE DCOM- 20070912 LR - 20161124 IS - 0959-6658 (Print) IS - 0959-6658 (Linking) VI - 17 IP - 7 DP - 2007 Jul TI - Trypanosome trans-sialidase mediates neuroprotection against oxidative stress, serum/glucose deprivation, and hypoxia-induced neurite retraction in Trk-expressing PC12 cells. PG - 725-34 AB - 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 TSDeltaAsp98-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 PC12(nnr5) cells, but are re-established in PC12(nnr5) 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. FAU - Woronowicz, Alicja AU - Woronowicz A AD - Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada K7L3N6. FAU - Amith, Schammim Ray AU - Amith SR FAU - Davis, Vanessa W AU - Davis VW FAU - Jayanth, Preethi AU - Jayanth P FAU - De Vusser, Kristof AU - De Vusser K FAU - Laroy, Wouter AU - Laroy W FAU - Contreras, Roland AU - Contreras R FAU - Meakin, Susan O AU - Meakin SO FAU - Szewczuk, Myron R AU - Szewczuk MR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070327 PL - England TA - Glycobiology JT - Glycobiology JID - 9104124 RN - 0 (Enzyme Inhibitors) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glycoproteins) RN - 20O93L6F9H (Oseltamivir) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.2.1.- (trans-sialidase) RN - EC 3.2.1.18 (Neuraminidase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Survival MH - Enzyme Inhibitors/pharmacology MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Glucose/*metabolism MH - Glycoproteins/*metabolism MH - Hypoxia MH - Nerve Growth Factor/metabolism MH - Neuraminidase/*metabolism MH - Oseltamivir/pharmacology MH - *Oxidative Stress MH - PC12 Cells MH - Rats MH - Receptor, trkB/*metabolism MH - Serum/*metabolism MH - Trypanosoma cruzi/*metabolism EDAT- 2007/03/29 09:00 MHDA- 2007/09/13 09:00 CRDT- 2007/03/29 09:00 PHST- 2007/03/29 09:00 [pubmed] PHST- 2007/09/13 09:00 [medline] PHST- 2007/03/29 09:00 [entrez] AID - cwm034 [pii] AID - 10.1093/glycob/cwm034 [doi] PST - ppublish SO - Glycobiology. 2007 Jul;17(7):725-34. doi: 10.1093/glycob/cwm034. Epub 2007 Mar 27.