Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Strassburger, M; Bloch, W; Sulyok, S; Schüller, J; Keist, AF; Schmidt, A; Wenk, J; Peters, T; Wlaschek, M; Lenart, J; Krieg, T; Hafner, M; Kümin, A; Werner, S; Müller, W; Scharffetter-Kochanek, K.
Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo.
Free Radic Biol Med. 2005; 38(11):1458-1470
Doi: 10.1016/j.freeradbiomed.2005.02.009
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Lenart Jacek
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- Abstract:
- To circumvent the early lethality of manganese superoxide dismutase (SOD2)-deficient mice, we have used a skin-specific strategy with introduction of loxP sites flanking exon 3 of the SOD2 gene. To our surprise, when breeding a female keratin 14 Cre transgenic mouse to a SOD2 "floxed" male mouse, due to keratin 14 promoter-driven Cre expression in the oocytes, all offspring were heterozygous for SOD2. In sharp contrast to initial publications on SOD2(+/-) mice, the herein reported mice on a mixed genetic background (C57BL/6 x 129/Ola) in their heterozygous state (SOD(+/-)) revealed distinct ultrastructural damage of the myocard, with swelling and disruption of mitochondria and accumulation of lipid droplets, increased nitrotyrosine formation, and lipid peroxidation as well as activation of apoptosis signaling pathways in the heart in vivo. Strikingly, and so far unreported, we found a substantial decrease in the activity of the cytosolic copper, zinc superoxide dismutase (SOD1) in the heart tissue of SOD2(+/-) mice, suggesting that the breakdown of mitochondrial membranes in the heart of SOD2(+/-) mice results in the enhanced release of superoxide anion radicals or derivatives thereof with subsequent inactivation of cytosolic SOD1. This model may be particularly suited to long-term studies on age-related heart failure as well as other age-related diseases and the polygenic base of tissue-specific responses to oxidative injury.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Blotting, Western -
- Electrophoresis, Polyacrylamide Gel -
- Embryo, Mammalian - cytology
- Female - cytology
- Genetic Vectors - cytology
- Glutathione Peroxidase - metabolism
- Heterozygote - metabolism
- Immunohistochemistry - metabolism
- Integrases - metabolism
- Lipid Peroxidation - metabolism
- Male - metabolism
- Mice - metabolism
- Mice, Inbred C57BL - metabolism
- Mice, Transgenic - metabolism
- Models, Genetic - metabolism
- Myocardium - metabolism
- Oocytes - metabolism
- Oxidative Stress - metabolism
- Oxygen - metabolism
- Phenotype - metabolism
- Promoter Regions (Genetics) - metabolism
- RNA - metabolism
- RNA, Messenger - metabolism
- Recombination, Genetic - metabolism
- Ribonucleases - metabolism
- Signal Transduction - metabolism
- Stem Cells - cytology
- Superoxide Dismutase - genetics
- Tyrosine - analogs and derivatives
- Find related publications in this database (Keywords)
- free radicals
- manganese superoxide dismutase
- copper
- zinc superoxide dismutase
- reactive oxygen species
- superoxide anion
- apoptosis
- heart tissue
- mouse model