3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Inhibition of nerve growth factor signaling by peroxynitrite.

      1 ,
      Journal of neuroscience research
      Wiley-Blackwell

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The reactive oxygen species peroxynitrite has been implicated in mediating oxidative damage within the brain, and in particular in those regions associated with the pathology of Alzheimer disease. Evidence for peroxynitrite damage includes the abundance of nitrated tyrosine residues within proteins of neural cells. Potential sites for peroxynitrite-induced cytotoxicity are the tyrosine residues of tyrosine kinase receptors that are crucial for the maintenance of cholinergic neurons. The peroxynitrite generator 3-morpholinosydnonmine (SIN-1) was used to examine the effects of peroxynitrite generation on nerve growth factor (NGF)/TrkA signaling in PC12 pheochromocytoma cells that express a cholinergic phenotype. NGF produced a concentration-dependent increase in PC12 cellular metabolism (EC(50) = 15.2 ng/ml) measured in a microphysiometer. This action of NGF was inhibited in a concentration-dependent manner up to 67% of control by a brief (20 min) exposure of the cells to SIN-1. This inhibition of the NGF cellular response by SIN-1 was not related to generalized cellular toxicity. In fact, the peroxynitrite scavenger uric acid significantly attenuated the inhibitory actions of SIN-1. Pretreatment with SIN-1 also resulted in a decrease in the NGF-induced phosphorylation of TrkA protein. Furthermore, SIN-1 treatment reduced the activity of mitogen activated protein kinase (MAPK), a downstream kinase activated by TrkA receptor stimulation. These data suggest that SIN-1 treatment inhibits NGF signaling by inactivating TrkA receptors through the formation of nitrotyrosine residues on the receptor. The inactivation of TrkA receptors may contribute to the initial insult that eventually leads to neuronal cell death.

          Related collections

          Author and article information

          Journal
          J. Neurosci. Res.
          Journal of neuroscience research
          Wiley-Blackwell
          0360-4012
          0360-4012
          Jan 01 2001
          : 63
          : 1
          Affiliations
          [1 ] Alzheimer Research Center, Department of Pharmacology and Toxicology, Department of Veterans Affairs Medical Center, Medical College of Georgia, Augusta, Georgia 30912-2300, USA.
          Article
          10.1002/1097-4547(20010101)63:1<27::AID-JNR4>3.0.CO;2-#
          10.1002/1097-4547(20010101)63:1<27::AID-JNR4>3.0.CO;2-#
          11169611
          489ab2ba-97b1-42a5-ad4d-06eaf70aeff7
          History

          Comments

          Comment on this article