Publication
Title
Role of oxidative stress in cardiac dysfunction of mice
Author
Abstract
This study was designed to determine the effects of PPAR alpha lack on cardiac mechanical performance and to identify potential intracellular mechanisms linking PPAR alpha pathway deficiency to cardiac contractile dysfunction. Echocardiography, ex vivo papillary muscle assays, and in vitro motility assays were used to assess global, intrinsic ventricular muscle performance and myosin mechanical properties, respectively, in PPAR alpha(-/-) and age-matched wild-type mice. Three-nitrotyrosine formation and 4-hydroxy-2-nonenal protein-adducts, both markers of oxidative damage, were analyzed by Western blot analysis and immunolabeling. Radical scavenging capacity was analyzed by measuring protein levels and/or activities of the main antioxidant enzymes, including catalase, glutathione peroxidase, and manganese and copper-inc superoxide dismutases. Echocardiographic left ventricular fractional shortening in PPAR alpha(-/-) was 16% lower than that in wild-type. Ex vivo left ventricular papillary muscle exhibited reduced shortening velocity and isometric tension (three-and two-fold, respectively). In vitro myosin-based velocity was approximate to 20% slower in PPAR alpha(-/-), indicating that myosin itself was involved in the contractile dysfunction. Staining of 3-nitrotyrosine was more pronounced in PPAR alpha(-/-), and myosin heavy chain was the main nitrated protein. Formation of 3-nitrotyrosine myosin heavy chain was twofold higher in PPAR alpha(-/-) and 4-hydroxy-2-nonenal protein-adducts were threefold higher. The expression and activity of manganese superoxide dismutase were respectively 33% and 50% lower in PPAR alpha(-/-), with no changes in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase. These findings demonstrate that PPAR alpha pathway deficiency impairs cardiac function and also identify oxidative damage to myosin as a link between PPAR alpha deficiency and contractile dysfunction.
Language
English
Source (journal)
American journal of physiology : heart and circulatory physiology / American Physiological Society. - Bethesda, Md, 1977, currens
Publication
Bethesda, Md : 2007
ISSN
0363-6135 [print]
0363-6135
1522-1539 [online]
DOI
10.1152/AJPHEART.00037.2007
Volume/pages
293 :1 (2007) , p. H93-H102
ISI
000247968800015
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
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Creation 03.01.2013
Last edited 17.12.2021
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