Mecanismo protector antioxidante de tiorredoxina 1 (Trx1) en el miocardio de ratones sépticos
Taking into account that myocardial dysfunction is associated with oxidative and nitrosative stress, we decided to study the protective role of Trx-1 in sepsis-induced myocardial dysfunction. Transgenic mice with cardiac specific over-expression (Tg-trx1) and its wildtype (WT) were subjected to ceca...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1174 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1174.dir/1174.PDF |
| Aporte de: |
| Sumario: | Taking into account that myocardial dysfunction is associated with oxidative and nitrosative stress, we decided to study the protective role of Trx-1 in sepsis-induced myocardial dysfunction. Transgenic mice with cardiac specific over-expression (Tg-trx1) and its wildtype (WT) were subjected to cecal ligation and double puncture or sham operation. After 6, 18, and 24 h, activity of antioxidants and mitochondrial chain electron transport enzymes were evaluated. Apoptosis and autophagy were measured by TUNEL assay, western blot and electronic microscopy, and mitochondrial dynamics and biogenesis by RT-qPCRand western blot. Inotropism and contractile reserve after ?-adrenergic stimulus was evaluated by the Langendorff technique. The results showed that Trx1 increases survival. In early sepsis attenuates the drop in contractile reserve, and in late sepsis it keeps less oxidative environment in the cell, delaying exhaustion of mitochondrial antioxidant capacity and loss of mitochondrial complex I activity. In addition, Trx1 reduces the percentage of mitochondria with morphologic alterations, the changes in mitochondrial dynamics, and significantly activates mitochondrial biogenesis and autophagy. It is concluded that in sepsis-induced myocardial dysfunction, Trx1 extends redox protection, preserving contractile reserve, delaying mitochondrial damage, and activating mechanisms of mitochondrial replacement, resulting in increased survival. |
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