Involvement of altered cytoskeletal protein phosphorylation in aluminum-induced CNS dysfunction.
In the present investigation, we have studied the effects of aluminum (10 mg/kg of body weight per day, i.p.) and desferrioxamine (6 mg/kg of body weight per day, i.p.) alone and in combination for 4 weeks on the regulation of phosphorylation of neuronal proteins. A marked decrease in the biological activity of calmodulin was observed after aluminum treatment; however, in combination with desferrioxamine, a reversal in the levels of calmodulin, in terms of nmol cAMP hydrolyzed/min/mg protein, was observed. Exogenous addition of calmodulin had an inhibitory effect on calmodulin-mediated synaptosomal protein phosphorylation in aluminum-exposed animals. An almost complete reversal of this inhibition was observed following coexposure to aluminum and desferrioxamine. Cyclic AMP-dependent synaptosomal protein phosphorylation was, however, stimulated following aluminum exposure. Coadministration of desferrioxamine along with aluminum was found to mitigate the neurotoxic effect of aluminum.
Julka
D
D
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Gill
K D
KD
D000535:Aluminum / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D001923:Brain Chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D007274:Injections, Intraperitoneal; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D000931:Antidotes; D002147:Calmodulin; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D000535:Aluminum; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003676:Deferoxamine