Altered calcium homeostasis: a possible mechanisms of aluminium-induced neurotoxicity.
The effect of aluminium, A1(3+) (10 mg/kg body weight/day i.p.) for a period of 4 weeks was examined on the calcium homeostatic mechanisms in rat central nervous system. Incubation of synaptosomes prepared from rat brain, with aluminium in vitro had a detrimental effect on the activity of Ca2+ ATPase which could be reversed completely on exogenous addition of desferrioxamine (10 microM) and partially with glutathione (1 mM). In vivo administration also revealed a similar observation. A marked increase in the levels of intracellular calcium was observed after aluminium treatment. Concomitant to the increased levels of intracellular calcium, there was an increase in the levels of lipid peroxidation and a consequent decrease in fluidity of synaptic plasma membranes. In addition, aluminium also had an inhibitory effect on the depolarization-induced calcium uptake which was found to be of a competitive type. The biological activity of calcium regulatory proteins calmodulin and protein kinase C was considerably affected by aluminium. The results suggest that aluminium exerts its toxic effects by modification of the intracellular calcium messenger system with detrimental consequences on neuronal functioning.
Julka
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Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Gill
K D
KD
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000535:Aluminum / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D002147:Calmodulin; D000535:Aluminum; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000252:Calcium-Transporting ATPases; D005978:Glutathione; D003676:Deferoxamine; D011188:Potassium; D002118:Calcium