Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress

Viviana I. Pérez, Christie M. Lew, Lisa A. Cortez, Celeste R. Webb, Marisela Rodriguez, Yuhong Liu, Wenbo Qi, Yan Li, Asish Chaudhuri, Holly Van Remmen, Arlan Richardson, Yuji Ikeno

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

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 ∼50% decrease in Trx-2 protein expression in all tissues without upregulating other the 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.

Original languageEnglish (US)
Pages (from-to)882-892
Number of pages11
JournalFree Radical Biology and Medicine
Volume44
Issue number5
DOIs
StatePublished - Mar 1 2008

Keywords

  • Mitochondrial function
  • Oxidative damage
  • ROS production
  • Thioredoxin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Pérez, V. I., Lew, C. M., Cortez, L. A., Webb, C. R., Rodriguez, M., Liu, Y., Qi, W., Li, Y., Chaudhuri, A., Van Remmen, H., Richardson, A., & Ikeno, Y. (2008). Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress. Free Radical Biology and Medicine, 44(5), 882-892. https://doi.org/10.1016/j.freeradbiomed.2007.11.018