In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase.
Cholinesterases are a large family of enzymatic proteins widely distributed throughout both neuronal and non-neuronal tissues. In Alzheimer's disease (AD), analytical as well as epidemiological studies suggest an implication of an abnormal focal accumulation of aluminum in the brain. In this devastating disease, aluminum may interfere with various biochemical processes including acetylcholine metabolism, and can thus act as a possible etiopathogenic cofactor. Acetylcholinesterase (AChE) exists in several molecular forms that differ in solubility and mode of membrane attachment rather than in catalytic activity. Mice were treated orally with aluminum chloride or aluminum lactate (Al(lac)(3)), and AChE activity in their brain homogenates was then assayed. Results showed that this in vivo treatment augmented the activity of the enzyme. An activating effect was also observed in vitro, when the aluminum compounds were added directly to mouse brain homogenates. However, the activating effect observed in vivo was much more marked than that observed in vitro. In addition, the activation produced by Al(lac)(3) was higher than that obtained after aluminum chloride treatment. Kinetics measurements of AChE activity in the absence and presence of treatment with aluminum both in vivo and in vitro are reported. The influence of the metal speciation on enzymatic activity is discussed in relation to a possible implication of aluminum in some neurodegenerative diseases.
Zatta
P
P
Department of Biology, CNR-Center on Metalloproteins, University of Padova, Padova, Italy. zatta@cribi1.bio.unipd.it
Ibn-Lkhayat-Idrissi
M
M
Zambenedetti
P
P
Kilyen
M
M
Kiss
T
T
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002712:Chlorides / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002802:Cholinesterases / Q000494:pharmacology; D007773:Lactates / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D013347:Subcellular Fractions; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013619:Tacrine / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D007773:Lactates; D000077410:Aluminum Chloride; D013619:Tacrine; D000110:Acetylcholinesterase; D002802:Cholinesterases; D000109:Acetylcholine; C104223:aluminum lactate