title: Aluminum interaction with human brain tau protein phosphorylation by various kinases.
abstract: 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.
authors.affiliation: Environmental Chem. and Toxicol. Lab., Texas Southern University, Houston 77004.
authors.forename: A H
authors.initials: AH
authors.lastname: el-Sebae
authors.forename: M E
authors.initials: ME
authors.lastname: Abdel-Ghany
authors.forename: D
authors.initials: D
authors.lastname: Shalloway
authors.forename: M M
authors.initials: MM
authors.lastname: Abou Zeid
authors.forename: J
authors.initials: J
authors.lastname: Blancato
authors.forename: M A
authors.initials: MA
authors.lastname: Saleh
mesh_terms: 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*
chemical_list: 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