Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain.
Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since it is well known that Hg vapor (Hg0) is continuously released from "silver" amalgam tooth fillings and is absorbed into brain, rats were exposed to Hg0 4h/day for 0, 2, 7, 14 and 28 d at 250 or 300 micrograms Hg/m3 air, concentrations present in mouth air of some humans with many amalgam fillings. Average rat brain Hg concentrations increased significantly (11-47 fold) with duration of Hg0 exposure. By 14 d Hg0 exposure, photoaffinity labelling on the beta-subunit of the tubulin dimer with [alpha 32P] 8N3 GTP in brain homogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzheimer brain homogenates from approximately 80% of patients, when compared to human age-matched neurological controls. Total tubulin protein levels remained relatively unchanged between Hg0 exposed rat brains and controls, and between Alzheimer brains and controls. Since the rate of tubulin polymerization is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.
Pendergrass
J C
JC
College of Pharmacy, University of Kentucky, Lexington 40536, USA.
Haley
B E
BE
Vimy
M J
MJ
Winfield
S A
SA
Lorscheider
F L
FL
D000280:Administration, Inhalation; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D003723:Dental Amalgam / Q000032:analysis / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D008297:Male; D008628:Mercury / Q000008:administration & dosage / Q000633:toxicity*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D003723:Dental Amalgam; D006160:Guanosine Triphosphate; D008628:Mercury