Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis

Exposure of plasma from apolipoprotein E gene knockout (apoE–/–) and control (CBA or C57BL/6J) mice plasma to a constant rate of aqueous peroxyl radicals (ROO.) resulted in the depletion of ascorbate, urate and α-tocopherol (α-TOH), with substantial and little lipid peroxidation, respectively. α-TOH...

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Main Authors: Jiří Neužil, Julie K. Christison, Eugene Iheanacho, Jean-Charles Fragonas, Vivienne Zammit, Nicholas H. Hunt, Roland Stocker
Format: Article
Language:English
Published: Elsevier 1998-02-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520338979
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author Jiří Neužil
Julie K. Christison
Eugene Iheanacho
Jean-Charles Fragonas
Vivienne Zammit
Nicholas H. Hunt
Roland Stocker
author_facet Jiří Neužil
Julie K. Christison
Eugene Iheanacho
Jean-Charles Fragonas
Vivienne Zammit
Nicholas H. Hunt
Roland Stocker
author_sort Jiří Neužil
collection DOAJ
description Exposure of plasma from apolipoprotein E gene knockout (apoE–/–) and control (CBA or C57BL/6J) mice plasma to a constant rate of aqueous peroxyl radicals (ROO.) resulted in the depletion of ascorbate, urate and α-tocopherol (α-TOH), with substantial and little lipid peroxidation, respectively. α-TOH levels were 3-times higher in plasma from apoE–/– than control mice and its addition enhanced the oxidizability of control mouse plasma. In apoE–/– mouse plasma, α-TOH was associated primarily with very low density lipoprotein (VLDL), whereas in plasma from control mice, the vitamin was located largely in high density lipoproteins. Oxidation of isolated lipoproteins by ROO. resulted in the accumulation of lipid hydroperoxides to an extent that reflected the plasma concentration and α-TOH content of the different lipoprotein fractions. Oxidation of 'plasma’ reconstituted from components of apoE–/– mice and/or human plasma showed that human and apoE–/– mouse lipoproteins peroxidized with similar kinetics, although the initiation of lipid peroxidation was greater in the presence of mouse than human lipoprotein-deficient plasma. Also, the chain length of lipid peroxidation in apoE–/– mouse plasma after ascorbate depletion appeared to be independent of the rate of ROO. generation. Together, these results show that the ROO. induced peroxidation of plasma lipoproteins in atherogenesis-susceptible apoE–/– mice exhibits some, though not all, features of tocopherol-mediated peroxidation (TMP). Therefore, apoE–/– mice may represent a suitable animal model to test a role for TMP in atherogenesis and the prevention of this disease by anti-TMP agents.—Neuzil, J., J. K. Christison, E. Iheanacho, J-C. Fragonas, V. Zammit, N. H. Hunt, and R. Stocker. Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis.
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spelling doaj.art-57f26017bda24ec2a32f9afe4b5812522022-12-21T21:28:50ZengElsevierJournal of Lipid Research0022-22751998-02-01392354368Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesisJiří Neužil0Julie K. Christison1Eugene Iheanacho2Jean-Charles Fragonas3Vivienne Zammit4Nicholas H. Hunt5Roland Stocker6Biochemistry Unit, Heart Research Institute, 145 Missenden Road, Camperdown, NSW 2050, AustraliaBiochemistry Unit, Heart Research Institute, 145 Missenden Road, Camperdown, NSW 2050, AustraliaDepartment of Pathology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Pathology, University of Sydney, Sydney, NSW 2006, AustraliaBiochemistry Unit, Heart Research Institute, 145 Missenden Road, Camperdown, NSW 2050, AustraliaDepartment of Pathology, University of Sydney, Sydney, NSW 2006, AustraliaBiochemistry Unit, Heart Research Institute, 145 Missenden Road, Camperdown, NSW 2050, Australia; To whom correspondence should be addressed.Exposure of plasma from apolipoprotein E gene knockout (apoE–/–) and control (CBA or C57BL/6J) mice plasma to a constant rate of aqueous peroxyl radicals (ROO.) resulted in the depletion of ascorbate, urate and α-tocopherol (α-TOH), with substantial and little lipid peroxidation, respectively. α-TOH levels were 3-times higher in plasma from apoE–/– than control mice and its addition enhanced the oxidizability of control mouse plasma. In apoE–/– mouse plasma, α-TOH was associated primarily with very low density lipoprotein (VLDL), whereas in plasma from control mice, the vitamin was located largely in high density lipoproteins. Oxidation of isolated lipoproteins by ROO. resulted in the accumulation of lipid hydroperoxides to an extent that reflected the plasma concentration and α-TOH content of the different lipoprotein fractions. Oxidation of 'plasma’ reconstituted from components of apoE–/– mice and/or human plasma showed that human and apoE–/– mouse lipoproteins peroxidized with similar kinetics, although the initiation of lipid peroxidation was greater in the presence of mouse than human lipoprotein-deficient plasma. Also, the chain length of lipid peroxidation in apoE–/– mouse plasma after ascorbate depletion appeared to be independent of the rate of ROO. generation. Together, these results show that the ROO. induced peroxidation of plasma lipoproteins in atherogenesis-susceptible apoE–/– mice exhibits some, though not all, features of tocopherol-mediated peroxidation (TMP). Therefore, apoE–/– mice may represent a suitable animal model to test a role for TMP in atherogenesis and the prevention of this disease by anti-TMP agents.—Neuzil, J., J. K. Christison, E. Iheanacho, J-C. Fragonas, V. Zammit, N. H. Hunt, and R. Stocker. Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis.http://www.sciencedirect.com/science/article/pii/S0022227520338979antioxidantsatherosclerosislipid peroxidationvitamin E
spellingShingle Jiří Neužil
Julie K. Christison
Eugene Iheanacho
Jean-Charles Fragonas
Vivienne Zammit
Nicholas H. Hunt
Roland Stocker
Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
Journal of Lipid Research
antioxidants
atherosclerosis
lipid peroxidation
vitamin E
title Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
title_full Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
title_fullStr Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
title_full_unstemmed Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
title_short Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE–/–) mice: apoE–/– mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis
title_sort radical induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein e gene knockout apoe mice apoe mouse as a model for testing the role of tocopherol mediated peroxidation in atherogenesis
topic antioxidants
atherosclerosis
lipid peroxidation
vitamin E
url http://www.sciencedirect.com/science/article/pii/S0022227520338979
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