PMID- 11095525 OWN - NLM STAT- MEDLINE DCOM- 20010531 LR - 20220227 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 11 IP - 16 DP - 2000 Nov 9 TI - Nitric oxide activation of TrkB through peroxynitrite. PG - 3593-7 AB - NIH-3T3 cells stably transfected with TrkB, the receptor for brain-derived neurotrophic factor (BDNF), were used to study the effects of NO and peroxynitrite on TrkB. 3-Morpholinosydnonimine (SIN-1), a donor of NO and O2- which immediately react to form peroxynitrite, induced TrkB tyrosine phosphorylation in a dose-dependent relationship from 2 to 40 mM. TrkB phosphorylation by SIN-1 was blocked by superoxide dismutase, which converts O2 to H2O2 and prevents its reaction with NO to form peroxynitrite, and by K252a, an inhibitor of TrkB phosphorylation by BDNF. Treatment with NO or O2- alone did not activate TrkB. Treatment directly with 1-4 mM peroxynitrite resulted in a dose-dependent increase in tyrosine phosphorylation of TrkB. SIN-1 treatment induced tyrosine phosphorylation of phospholipase C-gamma1 (PLC-gamma1) and induced its binding with activated TrkB, similar to that seen with BDNF downstream signaling pathways. These studies demonstrate activation of TrkB through peroxynitrite. FAU - Yuen, E C AU - Yuen EC AD - Department of Neurology, University of Washington, Seattle 98195, USA. FAU - Gunther, E C AU - Gunther EC FAU - Bothwell, M AU - Bothwell M LA - eng GR - AG00649/AG/NIA NIH HHS/United States GR - NS33200/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Indole Alkaloids) RN - 0 (Isoenzymes) RN - 0 (Nitrates) RN - 0 (Nitric Oxide Donors) RN - 0 (Oxidants) RN - 0 (Recombinant Proteins) RN - 21820-51-9 (Phosphotyrosine) RN - 26404-66-0 (peroxynitric acid) RN - 31C4KY9ESH (Nitric Oxide) RN - 5O5U71P6VQ (linsidomine) RN - 97161-97-2 (staurosporine aglycone) RN - D46583G77X (Molsidomine) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) SB - IM MH - 3T3 Cells MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Carbazoles/pharmacology MH - Humans MH - Indole Alkaloids MH - Isoenzymes/metabolism MH - Mice MH - Molsidomine/analogs & derivatives/pharmacology MH - Nitrates/*pharmacology MH - Nitric Oxide/*physiology MH - Nitric Oxide Donors/pharmacology MH - Oxidants/pharmacology MH - Phospholipase C gamma MH - Phosphorylation MH - Phosphotyrosine/metabolism MH - Rats MH - Receptor, trkB/drug effects/*physiology MH - Recombinant Proteins/drug effects/metabolism/pharmacology MH - Superoxide Dismutase/pharmacology MH - Transfection MH - Type C Phospholipases/metabolism EDAT- 2000/11/30 11:00 MHDA- 2001/06/02 10:01 CRDT- 2000/11/30 11:00 PHST- 2000/11/30 11:00 [pubmed] PHST- 2001/06/02 10:01 [medline] PHST- 2000/11/30 11:00 [entrez] AID - 10.1097/00001756-200011090-00038 [doi] PST - ppublish SO - Neuroreport. 2000 Nov 9;11(16):3593-7. doi: 10.1097/00001756-200011090-00038.