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

doi:10.1016/j.freeradbiomed.2007.11.018

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 journal › Article › peer-review

100 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 language	English (US)
Pages (from-to)	882-892
Number of pages	11
Journal	Free Radical Biology and Medicine
Volume	44
Issue number	5
DOIs	https://doi.org/10.1016/j.freeradbiomed.2007.11.018
State	Published - Mar 1 2008

Keywords

Mitochondrial function
Oxidative damage
ROS production
Thioredoxin

ASJC Scopus subject areas

Physiology (medical)
Biochemistry

Access to Document

10.1016/j.freeradbiomed.2007.11.018

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

Pérez, VI, Lew, CM, Cortez, LA, Webb, CR, 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, vol. 44, no. 5, pp. 882-892. https://doi.org/10.1016/j.freeradbiomed.2007.11.018

@article{8bbaa613eb274abbb8aa0d7ed0ea205a,

title = "Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress",

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.",

keywords = "Mitochondrial function, Oxidative damage, ROS production, Thioredoxin",

author = "P{\'e}rez, {Viviana I.} and Lew, {Christie M.} and Cortez, {Lisa A.} and Webb, {Celeste R.} and Marisela Rodriguez and Yuhong Liu and Wenbo Qi and Yan Li and Asish Chaudhuri and {Van Remmen}, Holly and Arlan Richardson and Yuji Ikeno",

note = "Funding Information: This work was supported by Nathan Shock Center of Excellence Grant (1P30-AG13319) and a Merit Review grant (Y.I.) from the Department of Veteran Affairs. The authors wish to thank Dr. Florian Muller for his helpful discussions and critical reading of the manuscript and Ms. Corinne Price for her excellent editorial work.",

year = "2008",

month = mar,

day = "1",

doi = "10.1016/j.freeradbiomed.2007.11.018",

language = "English (US)",

volume = "44",

pages = "882--892",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier Inc.",

number = "5",

}

TY - JOUR

T1 - Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress

AU - Pérez, Viviana I.

AU - Lew, Christie M.

AU - Cortez, Lisa A.

AU - Webb, Celeste R.

AU - Rodriguez, Marisela

AU - Liu, Yuhong

AU - Qi, Wenbo

AU - Li, Yan

AU - Chaudhuri, Asish

AU - Van Remmen, Holly

AU - Richardson, Arlan

AU - Ikeno, Yuji

N1 - Funding Information: This work was supported by Nathan Shock Center of Excellence Grant (1P30-AG13319) and a Merit Review grant (Y.I.) from the Department of Veteran Affairs. The authors wish to thank Dr. Florian Muller for his helpful discussions and critical reading of the manuscript and Ms. Corinne Price for her excellent editorial work.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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.

AB - 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.

KW - Mitochondrial function

KW - Oxidative damage

KW - ROS production

KW - Thioredoxin

UR - http://www.scopus.com/inward/record.url?scp=39149137166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39149137166&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2007.11.018

DO - 10.1016/j.freeradbiomed.2007.11.018

M3 - Article

C2 - 18164269

AN - SCOPUS:39149137166

SN - 0891-5849

VL - 44

SP - 882

EP - 892

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this