Oral aluminum alters in vitro protein phosphorylation and kinase activities in rat brain.
Chronic, oral administration of aluminum to rats increases the in vivo concentration of cyclic AMP and the phosphorylation of microtubule-associated protein-2 (MAP-2) and the 200 kD neurofilament subunit (15,16). In the present study, the effect of this treatment on endogenous protein phosphorylation in soluble and particulate fractions prepared from cerebral cortices was examined. Chronic aluminum treatment significantly elevated the basal and cyclic AMP-dependent phosphorylation of 11-12 endogenous proteins in the soluble fraction prepared from cerebral cortices. Endogenous protein phosphorylation in the soluble fraction occurring in the presence of Ca++ alone or Ca++, phorbol 12-myristate 13-acetate and phosphatidylserine was not significantly altered by aluminum treatment. In the particulate fraction the phosphorylation of several proteins was significantly decreased by aluminum administration; however, the phosphorylation of the majority of protein substrates remained unaltered. Aluminum treatment did not alter the activities of cyclic AMP-dependent protein kinase or protein tyrosine kinase in the soluble and particulate fractions. The activity of Ca++/phospholipid-dependent protein kinase (protein kinase C) was increased in the particulate fraction of aluminum-fed rats. These results clearly demonstrate that specific effects on protein phosphorylation and protein kinase activities result from in vivo aluminum administration.
Johnson
G V
GV
Department of Neurology, University of Alabama, Birmingham 35294.
Cogdill
K W
KW
Jope
R S
RS
D000284:Administration, Oral; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D008297:Male; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009419:Nerve Tissue Proteins; D000535:Aluminum; D000242:Cyclic AMP; D011494:Protein Kinases