Aluminum interaction with human brain tau protein phosphorylation by various kinases.
Phosphorylation is an indispensable process for energy and signal transduction in biological systems. AlCl3 at 10 nM to 10 microM range activated in-vitro [gamma-32P]ATP phosphorylation of the brain (tau) tau protein in both normal human or E. coli expressed tau forms; in the presence of the kinases P34, PKP, and PKC. However, higher concentrations of ALCl3 inhibited the tau phosphorylation with P34, PKP, and PKC to a maximum at 1 mM level. AlCl3 at 100 microM to 500 microM range induced non-enzymatic phosphorylation of tau with gamma-ATP, gamma-GTP, and alpha-GTP. AlCl3 activated histone phosphorylation by P34 in a similar pattern. The hyperphosphorylation of tau by Al3+ was accompanied by molecular shift and mobility retardation in SDS-PAGE. This may demonstrate the mechanism of the longterm neurological effect of Al3+ in human brain leading to the formation of the neurofibrillary tangles related to Alzheimer's disease.
el-Sebae
A H
AH
Environmental Chem. and Toxicol. Lab., Texas Southern University, Houston 77004.
Abdel-Ghany
M E
ME
Shalloway
D
D
Abou Zeid
M M
MM
Blancato
J
J
Saleh
M A
MA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000494:pharmacology; D002712:Chlorides / Q000633:toxicity*; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D006160:Guanosine Triphosphate / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D010770:Phosphotransferases / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D017607:Aluminum Compounds; D002712:Chlorides; D006657:Histones; D011994:Recombinant Proteins; D016875:tau Proteins; D000077410:Aluminum Chloride; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C054566:protein kinase P; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase