%0 Journal Article
%T Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration
%A Nathalie Arnal
%A Omar Castillo
%A Mar赤a J. T. de Alaniz
%A Carlos A. Marra
%J International Journal of Alzheimer's Disease
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/645379
%X Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3ˋppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A汕(1每42)/(1每40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements. 1. Introduction It is well known that copper (Cu) is an essential transition metal for all living organisms, functioning as cofactor for many enzymes [1每3]. However, we and other laboratories have demonstrated in vivo and in vitro that excess inorganic Cu produces increased levels of reactive oxygen species (ROS) and damage to biomolecules, ultimately promoting cell death [4每7]. Humans are continuously at risk from excess Cu due to involuntary exposure to pollution (contaminated water, food), professional activities [8每10], ingestion of dietary supplements [10每12], and prolonged use of intrauterine devices [13, 14]. Elevated Cu plasma levels, especially of free-Cu or the so-called nonceruloplasmin-bound Cu (NCBC), have been associated with neurodegenerative damage [10, 15, 16]. In recent years, there has been a considerable increase in the number of published papers relating Cu to the neurodegenerative process [15每18]. In line with this, Brewer [10] hypothesized that ingestion of inorganic Cu from different sources is at least a partial cause of Alzheimer disease (AD) in developed countries. Squitti et al. [17每19] reported that NCBC, which is loosely bound to molecules such as serum albumin and other proteins, is one of the main risk factors
%U http://www.hindawi.com/journals/ijad/2013/645379/