title: Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease.
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.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
authors.forename: Kunjan R
authors.initials: KR
authors.lastname: Dave
authors.forename: Ami P
authors.initials: AP
authors.lastname: Raval
authors.forename: Jesús
authors.initials: J
authors.lastname: Purroy
authors.forename: Ilias G
authors.initials: IG
authors.lastname: Kirkinezos
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
authors.forename: Walter G
authors.initials: WG
authors.lastname: Bradley
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pérez-Pinzón
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008928:Mitochondria / Q000201:enzymology; D009044:Motor Cortex / Q000201:enzymology / Q000473:pathology; D016472:Motor Neuron Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009410:Nerve Degeneration / Q000201:enzymology / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport; D017966:Pyramidal Cells / Q000201:enzymology / Q000473:pathology; D011712:Pyramidal Tracts / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology
chemical_list: C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases