Phosphorylation-related immunoreactivity and the rate of transport of neurofilaments in chronic 2,5-hexanedione intoxication.
Axonal transport of neurofilaments and the phosphorylation of epitopes on neurofilament proteins was studied in rats chronically intoxicated with 2,5-hexanedione. Sensory axons arising from the L5 dorsal root ganglion exhibited accelerated transport and a reduced abundance of neurofilament proteins. The binding of an antibody to phosphorylated neurofilament epitopes was compared to the binding of an antibody to non-phosphorylated epitopes by quantitative ELISA. This immunochemical index of neurofilament phosphorylation was reduced in dorsal roots, proximal peripheral sensory axons and ventral roots, but not in a distal nerve (the nerve to the soleus). Axotomy produced a reduction in neurofilament protein abundance comparable to hexanedione without any change in the immunochemical phosphorylation index. These results are consistent with the hypothesis that the state of phosphorylation of neurofilaments in proximal axons is correlated with the rate of neurofilament transport.
Watson
D F
DF
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore MD 21205.
Fittro
K P
KP
Hoffman
P N
PN
Griffin
J W
JW
D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000187:drug effects / Q000502:physiology; D000939:Epitopes / Q000032:analysis; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006588:Hexanones / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D016900:Neurofilament Proteins; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity*; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D000939:Epitopes; D006588:Hexanones; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D009498:Neurotoxins; C011269:2,5-hexanedione