Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress
| Autor: | Arlan Richardson, Celeste R. Webb, Viviana I. Pérez, Marisela Rodriguez, Yuhong Liu, Yuji Ikeno, Christie M. Lew, Wenbo Qi, Yan Li, Asish R. Chaudhuri, Holly Van Remmen, Lisa A. Cortez |
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| Rok vydání: | 2008 |
| Předmět: |
Male
DNA damage Cell Respiration Apoptosis Mitochondria Liver Mitochondrion medicine.disease_cause DNA Mitochondrial Biochemistry Electron Transport Superoxide dismutase Mice Adenosine Triphosphate Thioredoxins Physiology (medical) medicine Animals Mice Knockout chemistry.chemical_classification Glutathione Peroxidase TXN2 Reactive oxygen species biology Superoxide Dismutase Proteins Hydrogen Peroxide Lipids Molecular biology Oxidative Stress Liver chemistry biology.protein Thioredoxin Reactive Oxygen Species Oxidative stress DNA Damage Subcellular Fractions |
| Zdroj: | Free Radical Biology and Medicine. 44:882-892 |
| ISSN: | 0891-5849 |
| Popis: | The mitochondrial form of thioredoxin, thioredoxin 2 (Txn2), plays an important role in redox control and protection against ROS-induced mitochondrial damage. To evaluate the effect of reduced levels of Txn2 in vivo, we measured oxidative damage and mitochondrial function using mice heterozygous for the Txn2 gene (Txn2(+/-)). The Txn2(+/-) mice showed approximately 50% decrease in Trx-2 protein expression in all tissues without upregulating the other major components of the antioxidant defense system. Reduced levels of Txn2 resulted in decreased mitochondrial function as shown by reduced ATP production by isolated mitochondria and reduced activity of electron transport chain complexes (ETCs). Mitochondria isolated from Txn2(+/-) mice also showed increased ROS production compared to wild type mice. The Txn2(+/-) mice showed increased oxidative damage to nuclear DNA, lipids, and proteins in liver. In addition, we observed an increase in apoptosis in liver from Txn2(+/-) mice compared with wild type mice after diquat treatment. Our results suggest that Txn2 plays an important role in protecting the mitochondria against oxidative stress and in sensitizing the cells to ROS-induced apoptosis. |
| Databáze: | OpenAIRE |
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