MnSOD overexpression reduces fibrosis and pro-apoptotic signaling in the aging mouse heart

Title
MnSOD overexpression reduces fibrosis and pro-apoptotic signaling in the aging mouse heart
Authors
곽효범
Keywords
Aging, Fibrosis., Heart, Oxidative stress, Superoxide dismutase
Issue Date
2015-05
Publisher
JOURNALS OF GERONTOLOGY, SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Series/Report no.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES ; Vol70 no.5 Startpage 533 Endpage 544
Abstract
Contractility of the heart is impaired with advancing age via mechanical remodeling, as myocytes are lost through apoptosis and collagenous fibers accumulate. Exercise training confers protection against fibrosis and apoptosis in the aging heart, but the mechanisms remain poorly understood. We recently reported that exercise training elevates Mn isoform of superoxide dismutase (MnSOD) in the aging heart, concomitant with reduction in oxidative stress and fibrosis. Here, we tested the hypothesis that overexpression of MnSOD would be causal in protection against fibrosis and apoptosis in the aging heart. Hearts were extracted from young (8 months) wild-type, young mice overexpressing the Sod2 (MnSOD) gene, old (28 months) wild-type, and old transgenic mice. Left ventricle MnSOD protein levels were elevated in young mice overexpressing the Sod2 (MnSOD) gene and old transgenic mice. MnSODTg mice exhibited lower oxidative stress (total hydroperoxides, 4-hydroxynonenal, and 8-isoprostane) in the old group. Age-related cardiac remodeling and fibrosis was mitigated in MnSOD Tg mice with reductions in extramyocyte space (-65%), collagen-I, and transforming growth factor-β. Pro-apoptotic markers Bax (-38%) and caspase-3 cleavage (-41%) were reduced and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei, DNA laddering) was mitigated in MnSOD Tg hearts compared with old wild-type. We conclude that MnSOD elevation is indeed protective against oxidative stress, fibrosis, and apoptosis in the aging heart.
URI
https://academic.oup.com/biomedgerontology/article/70/5/533/647153
http://dspace.inha.ac.kr/handle/10505/55168
ISSN
1079-5006
Appears in Collections:
School of Arts & Sports(예술체육학부) > Kinesiology (스포츠과학) > Journal Papers (스포츠과학_학술논문)
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