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Manganese superoxide dismutase deficiency exacerbates the mitochondrial ROS production and oxidative damage in Chagas disease

Wen, Jake J ; Garg, Nisha Jain Tanowitz, Herbert B.

PLoS neglected tropical diseases, 2018-07, Vol.12 (7), p.e0006687-e0006687 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Manganese superoxide dismutase deficiency exacerbates the mitochondrial ROS production and oxidative damage in Chagas disease
Autor: Wen, Jake J ; Garg, Nisha Jain
Tanowitz, Herbert B.
Assuntos: 4-Hydroxynonenal ; Additives ; Adenosine diphosphate ; ADP ; Animals ; ATP ; Biology and Life Sciences ; Capacity ; Carbonyl compounds ; Carbonyls ; Cardiomyocytes ; Cardiomyopathy ; Chagas Cardiomyopathy - enzymology ; Chagas Cardiomyopathy - genetics ; Chagas Cardiomyopathy - metabolism ; Chagas Cardiomyopathy - parasitology ; Chagas' disease ; Chronic illnesses ; Chronic infection ; Complications and side effects ; Damage ; Deoxyribonucleic acid ; Disease ; Diseases ; DNA ; Electron transport chain ; Enzymes ; Female ; Gene expression ; Genetic aspects ; Genetic testing ; Health aspects ; Heart ; House mouse ; Humans ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; Immunology ; Infections ; Inflammation ; Inflammatory response ; Interleukin 6 ; L-Lactate dehydrogenase ; Lactate ; Lactate dehydrogenase ; Lactic acid ; Male ; Malondialdehyde ; Manganese ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria ; Mitochondria - genetics ; Mitochondria - metabolism ; Myocardial diseases ; Myocardium ; Myocardium - metabolism ; NADH-ubiquinone oxidoreductase ; Oxidative Phosphorylation ; Oxidative Stress ; Parasites ; Peroxidase ; Phosphorylation ; Proteins ; Protozoa ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Risk factors ; Superoxide dismutase ; Superoxide Dismutase - deficiency ; Superoxide Dismutase - genetics ; Superoxides ; Synthesis ; Tropical diseases ; Trypanosoma cruzi ; Trypanosoma cruzi - physiology ; Vector-borne diseases
É parte de: PLoS neglected tropical diseases, 2018-07, Vol.12 (7), p.e0006687-e0006687
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Current address: Department of Surgery, UTMB, Galveston, Texas, United States of America
The authors have declared that no competing interests exist.
Descrição: In this study, we have investigated the effects of manganese superoxide dismutase (SOD2 or MnSOD) deficiency on mitochondrial function and oxidative stress during Chagas disease. For this, C57BL/6 wild type (WT) and MnSOD+/- mice were infected with Trypanosoma cruzi (Tc), and evaluated at 150 days' post-infection that corresponded to chronic disease phase. Genetic deletion of SOD2 decreased the expression and activity of MnSOD, but it had no effect on the expression of other members of the SOD family. The myocardial expression and activity of MnSOD were significantly decreased in chronically infected WT mice, and it was further worsened in MnSOD+/- mice. Chronic T. cruzi infection led to a decline in mitochondrial complex I and complex II driven, ADP-coupled respiration and ATP synthesis in the myocardium of WT mice. The baseline oxidative phosphorylation (OXPHOS) capacity in MnSOD+/- mice was decreased, and it had an additive effect on mitochondrial dysregulation of ATP synthesis capacity in chagasic myocardium. Further, MnSOD deficiency exacerbated the mitochondrial rate of reactive oxygen species (ROS) production and myocardial oxidative stress (H2O2, protein carbonyls, malondialdehyde, and 4-hydroxynonenal) in Chagas disease. Peripheral and myocardial parasite burden and inflammatory response (myeloperoxidase, IL-6, lactate dehydrogenase, inflammatory infiltrate) were increased in all chagasic WT and MnSOD+/- mice. We conclude that MnSOD deficiency exacerbates the loss in mitochondrial function and OXPHOS capacity and enhances the myocardial oxidative damage in chagasic cardiomyopathy. Mitochondria targeted, small molecule mitigators of MnSOD deficiency will offer potential benefits in averting the mitochondrial dysfunction and chronic oxidative stress in Chagas disease.
Editor: United States: Public Library of Science
Idioma: Inglês

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Manganese superoxide dismutase deficiency exacerbates the mitochondrial ROS production and oxidative damage in Chagas disease

Wen, Jake J ; Garg, Nisha Jain Tanowitz, Herbert B.

United States: Public Library of Science

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