Abstract
Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis / enzymology*
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / pathology
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Animals
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Caspase 3
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Caspases / metabolism*
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Disease Models, Animal
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Down-Regulation / physiology
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Enzyme Activation
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Female
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Immunohistochemistry
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Male
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Mice
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Mice, Neurologic Mutants
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Mitochondria / enzymology
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Motor Cortex / enzymology
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Motor Cortex / pathology
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Motor Neuron Disease / enzymology*
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Motor Neuron Disease / genetics
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Motor Neuron Disease / pathology
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Motor Neurons / enzymology*
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Motor Neurons / pathology
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Nerve Degeneration / enzymology
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Nerve Degeneration / pathology
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Protein Kinase C / genetics
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Protein Kinase C / metabolism*
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Protein Kinase C-delta
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Protein Transport
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Pyramidal Cells / enzymology
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Pyramidal Cells / pathology
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Pyramidal Tracts / enzymology
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Pyramidal Tracts / pathology
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Signal Transduction / physiology
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Spinal Cord / enzymology*
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Spinal Cord / pathology
Substances
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Prkcd protein, mouse
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Protein Kinase C
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Protein Kinase C-delta
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Casp3 protein, mouse
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Caspase 3
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Caspases