Specific non-enzymatic glycation of the rat histone H1 nucleotide binding site in vitro in the presence of AlF4-. A putative mechanism for impaired chromatin function.
We show here that an aluminium derivative, AlF4-, stimulates glycation of histone H1 selectively in the proximity of its nucleotide-binding site. This adduct formation interferes with nucleoside triphosphate hydrolysis by H1 and with nucleotide modulation of H1 DNA binding. The present mode of aluminium action may in part be responsible for its effects on the chromatin structure and expression of tissue-specific genes, and may constitute a mechanism in the pathogenesis of aluminium-induced encephalopathy and in that of Alzheimer's disease, for example.
Tarkka
T
T
Collagen Research Unit, University of Oulu, Finland.
Yli-Mäyry
N
N
Mannermaa
R M
RM
Majamaa
K
K
Oikarinen
J
J
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005459:Fluorides; D005461:Fluorine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
D017607:Aluminum Compounds; D002843:Chromatin; D006657:Histones; D009711:Nucleotides; C050992:tetrafluoroaluminate; D005461:Fluorine; D004247:DNA; D000535:Aluminum; D005947:Glucose; D005459:Fluorides