Abstract
Application of nerve growth factor (NGF) covalently cross-linked to beads increased the phosphorylation of TrkA and Akt, but not of mitogen-activated protein kinase, in cultured rat sympathetic neurons. NGF beads or iodine-125-labeled NGF beads supplied to distal axons resulted in the survival of over 80% of the neurons for 30 hours, with little or no retrograde transport of iodine-125-labeled NGF; whereas application of free iodine-125-labeled NGF (0.5 nanograms per milliliter) produced 20-fold more retrograde transport, but only 29% of the neurons survived. Thus, in contrast to widely accepted theory, a neuronal survival signal can reach the cell bodies unaccompanied by the NGF that initiated it.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / metabolism*
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Cell Survival / drug effects
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Cells, Cultured
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Chromones / pharmacology
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Cross-Linking Reagents
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Enzyme Inhibitors / pharmacology
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Iodine Radioisotopes
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Microspheres
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Mitogen-Activated Protein Kinases / metabolism
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Morpholines / pharmacology
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Nerve Growth Factor / metabolism*
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Nerve Growth Factor / pharmacology
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Neurons / metabolism
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Neurons / physiology*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Protein Transport
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Rats, Sprague-Dawley
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Receptor, trkA / metabolism
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Signal Transduction
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Superior Cervical Ganglion
Substances
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Chromones
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Cross-Linking Reagents
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Enzyme Inhibitors
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Iodine Radioisotopes
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Nerve Growth Factor
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Receptor, trkA
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases