Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

Aluminium as a cell membrane menace
INTRODUCTION
Numerous studies performed both in vitro and in vivo considered that the
principal consequences of aluminium on the cerebral functions are mediated through
damage to cell membranes. Metals without redox capacity as aluminium were suggested
to make fatty acids more available to the action of free radicals and therefore ease the
spread of lipid peroxidation (Oteiza et al. 1993a, Ohyashiki et al. 1998).
Actually, aluminium binds to membrane components and modifies both
membrane biophysical properties and dynamics. Binding of aluminium is enhanced by
the presence of polar head groups with negative charge and happens via formation of
both cis and trans complexes (Oteiza 1994, Verstraeten 2000). This metal was shown to
bind through electrostatic interactions preferentially to the phosphatidylserine,
phosphatidic acid, and poliphosphoinositides found in biological membranes because of
their overall negative charge due to their carboxylate or phosphate moieties. Trans-
interactions or intervesicle interactions are not specifically implicated in lipid oxidation
as they result in membrane aggregation and fusion (Verstaeten and Oteiza 1995).
Actually, superficial charges are neutralized by aluminium which causes the
intercrossing and dehydration of neighboring phosphatidylserine molecules. On the
other hand, cis-interactions within the same vesicle lead to the lateral reorganization of
these phospholipids (lipid clustering) and formation of distinct microdomains enriched
in acidic phospholipids with lower membrane fluidity (Verstraeten and Oteiza 1995,
Verstraeten et al. 1997a, 1998). The local accumulation of poly-unsaturated fatty acids
caused by aluminium makes the phospholipids higly susceptible to ROS, leading to the
propagation of lipid peroxidation.
Aluminium was also shown to modify the biophysical properties of membranes
containing galactocerebrosides or polyphosphoinositides (Verstraeten et al. 1998, 2003,
Verstraeten and Oteiza 2002), myelin and synaptosomal membranes, which may result
in injurious effects for neurotransmission (Ohba et al. 1994, Julka and Gill 1996b,
Verstraeten et al. 1997b, Silva et al. 2002, Pandya et al. 2004).
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