title: A role for amplified protein kinase C activity in the pathogenesis of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a human neurodegenerative disorder of unknown origin that is characterized by progressive degeneration of corticospinal tracts and anterior horn cells in the brainstem and spinal cord. Previous studies have indicated that motoneuron degeneration associated with ALS may be triggered by mechanisms leading to increased intracellular Ca2+. In the present report, Ca(2+)-activated phospholipid-dependent protein kinase C (PKC) was evaluated in cervical spinal cords from ALS patients and control subjects. In patients who died with ALS, PKC histone H1 phosphotransferase activity was significantly increased by 330% in cytosolic- and 118% in particulate-derived extracts compared with controls. This increase in PKC phosphotransferase activity appeared to be partially due to an increase in the amount of PKC protein present in ALS spinal cord tissue. PKC histone H1 phosphotransferase activities of cytosolic- and particulate-derived extracts from motor and visual cortex of ALS patients and controls were not statistically different, nor were there differences in PKC histone H1 phosphotransferase activity in platelets and leukocytes. The specific nature of PKC alterations in affected regions of the CNS supports a role for PKC in the events leading to motoneuron death in sporadic ALS.
authors.affiliation: Neuroscience Programme, University of British Columbia, Vancouver, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Lanius
authors.forename: H B
authors.initials: HB
authors.lastname: Paddon
authors.forename: M
authors.initials: M
authors.lastname: Mezei
authors.forename: R
authors.initials: R
authors.lastname: Wagey
authors.forename: C
authors.initials: C
authors.lastname: Krieger
authors.forename: S L
authors.initials: SL
authors.lastname: Pelech
authors.forename: C A
authors.initials: CA
authors.lastname: Shaw
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D006801:Humans; D008875:Middle Aged; D009044:Motor Cortex / Q000201:enzymology; D009333:Neck; D010766:Phosphorylation; D006656:Protamine Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012016:Reference Values; D013116:Spinal Cord / Q000201:enzymology; D014793:Visual Cortex / Q000201:enzymology
chemical_list: D006656:Protamine Kinase; D011493:Protein Kinase C