Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/196188
Type: Artigo de periódico
Title: Oxidative Stress In Atherosclerosis-prone Mouse Is Due To Low Antioxidant Capacity Of Mitochondria.
Author: Oliveira, Helena C F
Cosso, Ricardo G
Alberici, Luciane C
Maciel, Evelise N
Salerno, Alessandro G
Dorighello, Gabriel G
Velho, Jesus A
de Faria, Eliana C
Vercesi, Aníbal E
Abstract: Atherosclerotic disease remains a leading cause of death in westernized societies, and reactive oxygen species (ROS) play a pivotal role in atherogenesis. Mitochondria are the main intracellular sites of ROS generation and are also targets for oxidative damage. Here, we show that mitochondria from atherosclerosis-prone, hypercholesterolemic low-density lipoprotein (LDL) receptor knockout mice have oxidative phosphorylation efficiency similar to that from control mice but have a higher net production of ROS and susceptibility to develop membrane permeability transition. Increased ROS production was observed in mitochondria isolated from several tissues, including liver, heart, and brain, and in intact mononuclear cells from spleen. In contrast to control mitochondria, knockout mouse mitochondria did not sustain a reduced state of matrix NADPH, the main source of antioxidant defense against ROS. Experiments in vivo showed faster liver secretion rates and de novo synthesis of triglycerides and cholesterol in knockout than in control mice, suggesting that increased lipogenesis depleted the reducing equivalents from NADPH and generated a state of oxidative stress in hypercholesterolemic knockout mice. These data provide the first evidence of how oxidative stress is generated in LDL receptor defective cells and could explain the increased LDL oxidation, cell death, and atherogenesis seen in familiar hypercholesterolemia.
Subject: Animals
Antioxidants
Arteriosclerosis
Brain
Female
Hypercholesterolemia
Ion Channels
Leukocytes, Mononuclear
Male
Mice
Mice, Knockout
Mitochondria
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Myocardium
Oxidative Stress
Reactive Oxygen Species
Receptors, Ldl
Spleen
Rights: fechado
Identifier DOI: 10.1096/fj.04-2095fje
Address: http://www.ncbi.nlm.nih.gov/pubmed/15569776
Date Issue: 2005
Appears in Collections:Unicamp - Artigos e Outros Documentos

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