Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Abstract

Background-Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. Methods and Results-We created MI in 12-to 16-week-old, male Prx-3-transgenic mice (TGϩMI, nϭ37) and nontransgenic wild-type mice (WTϩMI, nϭ39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TGϩMI than in WTϩMI mice (meanϮSEM, 1.5Ϯ0.2 vs 2.2Ϯ0.2 nmol/mg protein; nϭ8 each, PϽ0.05). LV cavity dilatation and dysfunction were attenuated in TGϩMI compared with WTϩMI mice, with no significant differences in infarct size (56Ϯ1% vs 55Ϯ1%; nϭ6 each, PϭNS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TGϩMI mice were also larger than those in WTϩsham-operated mice but smaller than those in WTϩMI mice. Improvement in LV function in TGϩMI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WTϩMI mice, and this decrease was also ameliorated in TGϩMI mice. Conclusions-Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.

Transgenic mitochondrial superoxide dismutase and mitochondrially targeted catalase prevent antiretroviral-induced oxidative stress and cardiomyopathy

“…8,9 Mitochondria eliminate H 2 O 2 primarily through the enzyme activity of glutathione peroxidase, 10 while oxidizing glutathione (GSH) to GSSG or through peroxiredoxins. [11][12][13] These enzymes prevent H 2 O 2 accumulation, limit formation of reactive species (eg, the hydroxyl radical, from H 2 O 2 reactions with reduced iron or copper 14 ), prevent left ventricular remodeling 11 and cardiotoxicity. 15 In peroxisomes, catalase is an enzyme that decomposes H 2 O 2 from flavoprotein reactions.…”

Molecular characterization and expression analysis of six peroxiredoxin paralogous genes in gilthead sea bream (Sparus aurata): Insights from fish exposed to dietary, pathogen and confinement stressors

“…This is, thereby, the first study, indentifying unequivocally six mammalian PRDX counterparts in a teleost fish. Importantly, the concomitant gene expression of mitochondrial PRDX3 and 5 was also addressed for the first time in fish, and this will serve to match the primary antioxidant defense of mitochondrial respiratory chain as evidenced in mice during the experimentally-induced myocardial infarction [43].…”

Estrés oxidativo: ¿un estado celular defectuoso para la función espermática?

“…Las implicaciones sobre cómo las mitocondrias producen ROS, son de vital importancia para entender una serie de temas biomédicos como la diabetes, el envejecimiento, la enfermedad de Alzheimer, la insuficiencia cardíaca, entre otras condiciones médicas asociadas (23)(24)(25). Los niveles basales de ROS y el papel de las mitocondrias en el mantenimiento de éstos aún se desconocen en las células germinales masculinas.…”