Nitric oxide activation of TrkB through peroxynitrite

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 phosphor...

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Veröffentlicht in:Neuroreport 2000-11, Vol.11 (16), p.3593-3597
Hauptverfasser: Yuen, Eric C, Gunther, Erik C, Bothwell, Mark
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Bothwell, Mark
description 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-γ1 (PLC-γ1) and induced its binding with activated TrkB, similar to that seen with BDNF downstream signaling pathways. These studies demonstrate activation of TrkB through peroxynitrite.
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Psychology</topic><topic>Humans</topic><topic>Indole Alkaloids</topic><topic>Isoenzymes - metabolism</topic><topic>Mice</topic><topic>Molsidomine - analogs &amp; derivatives</topic><topic>Molsidomine - pharmacology</topic><topic>Nitrates - pharmacology</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Oxidants - pharmacology</topic><topic>Phospholipase C gamma</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - metabolism</topic><topic>Rats</topic><topic>Receptor, trkB - drug effects</topic><topic>Receptor, trkB - physiology</topic><topic>Recombinant Proteins - drug effects</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Superoxide Dismutase - pharmacology</topic><topic>Transfection</topic><topic>Type C Phospholipases - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuen, Eric C</creatorcontrib><creatorcontrib>Gunther, Erik C</creatorcontrib><creatorcontrib>Bothwell, Mark</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroreport</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuen, Eric C</au><au>Gunther, Erik C</au><au>Bothwell, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide activation of TrkB through peroxynitrite</atitle><jtitle>Neuroreport</jtitle><addtitle>Neuroreport</addtitle><date>2000-11-09</date><risdate>2000</risdate><volume>11</volume><issue>16</issue><spage>3593</spage><epage>3597</epage><pages>3593-3597</pages><issn>0959-4965</issn><eissn>1473-558X</eissn><abstract>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. 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subjects 3T3 Cells
Animals
Biochemistry and metabolism
Biological and medical sciences
Brain-Derived Neurotrophic Factor - pharmacology
Carbazoles - pharmacology
Central nervous system
Fundamental and applied biological sciences. Psychology
Humans
Indole Alkaloids
Isoenzymes - metabolism
Mice
Molsidomine - analogs & derivatives
Molsidomine - pharmacology
Nitrates - pharmacology
Nitric Oxide - physiology
Nitric Oxide Donors - pharmacology
Oxidants - pharmacology
Phospholipase C gamma
Phosphorylation
Phosphotyrosine - metabolism
Rats
Receptor, trkB - drug effects
Receptor, trkB - physiology
Recombinant Proteins - drug effects
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Superoxide Dismutase - pharmacology
Transfection
Type C Phospholipases - metabolism
Vertebrates: nervous system and sense organs
title Nitric oxide activation of TrkB through peroxynitrite
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