From: Ian Goddard (Ian@Goddard.net)
Date: Tue Mar 06 2001 - 08:19:39 MST
Neurotoxicology 1997;18(2):315-24
Mercury vapor inhalation inhibits binding of GTP to tubulin in rat
brain: similarity to a molecular lesion in Alzheimer diseased brain.
Pendergrass JC, Haley BE, Vimy MJ, Winfield SA, Lorscheider FL
College of Pharmacy, University of Kentucky, Lexington 40536, USA.
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.
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