ACRYLAMIDE INCREASES IN-VITRO CALCIUM AND CALMODULIN-DEPENDENT KINASE-MEDIATED PHOSPHORYLATION OF RAT-BRAIN AND SPINAL-CORD NEUROFILAMENT PROTEINS

Male Sprague-Dawley rats were administered a daily i.p. dose of 0.70 m mol/kg body weight of acrylamide, propionamide (a non-neurotoxic struc tural analog of acrylamide) or deionized water. Animals were sacrifice d when signs of severe neurotoxicity were apparent. Neurofilaments (NF s) and endogenous kinase were isolated from the brain and spinal cord by axonal floatation. Increased in vitro Ca2+/calmodulin-dependent pho sphorylation of endogenous and exogenous NF proteins and autophosphory lation of Ca2+/calmodulin protein kinase II (CaM kinase II, EC 2-7-1-3 7) were observed in samples from both brain and spinal cord of acrylam ide-treated animals compared with controls. There was no significant d ifference between samples isolated from propionamide-treated animals a nd controls. Increased calmodulin binding to brain supernatant CaM kin ase II was also observed as a result of acrylamide treatment. There wa s no significant difference observed in the amount of antibody binding to the a-subunit of brain supernatant CaM kinase II between treated o r control animals. These results suggest that increased CaM kinase II- dependent phosphorylation of cytoskeletal proteins may be involved in the mechanisms of acrylamide-induced neurotoxicity.