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 mmol/kg body weight of acrylamide, propionamide (a non-neurotoxic structural analog of acrylamide) or deionized water. Animals were sacrificed when signs of severe neurotoxicity were apparent. Neurofilaments (NFs) and endogenous kinase were isolated from the brain and spinal cord by axonal floatation. Increased in vitro Ca2+/calmodulin-dependent phosphorylation of endogenous and exogenous NF proteins and autophosphorylation of Ca2+/calmodulin protein kinase II (CaM kinase II, EC 2-7-1-37) were observed in samples from both brain and spinal cord of acrylamide-treated animals compared with controls. There was no significant difference between samples isolated from propionamide-treated animals and controls. Increased calmodulin binding to brain supernatant CaM kinase II was also observed as a result of acrylamide treatment. There was no significant difference observed in the amount of antibody binding to the alpha-subunit of brain supernatant CaM kinase II between treated or 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.
Reagan
K E
KE
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Wilmarth
K R
KR
Friedman
M
M
Abou-Donia
M B
MB
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology* / Q000633:toxicity; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D000178:Acrylamides; D000577:Amides; D002147:Calmodulin; D016900:Neurofilament Proteins; D020106:Acrylamide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C034666:propionamide