Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress.
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.
Pérez
Viviana I
VI
The Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78229, USA.
Lew
Christie M
CM
Cortez
Lisa A
LA
Webb
Celeste R
CR
Rodriguez
Marisela
M
Liu
Yuhong
Y
Qi
Wenbo
W
Li
Yan
Y
Chaudhuri
Asish
A
Van Remmen
Holly
H
Richardson
Arlan
A
Ikeno
Yuji
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D019069:Cell Respiration; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013347:Subcellular Fractions; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*
D004272:DNA, Mitochondrial; D008055:Lipids; D011506:Proteins; D017382:Reactive Oxygen Species; C516112:Txn2 protein, mouse; D013879:Thioredoxins; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase