Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart

Tetsuro Ago, Ijen Yeh, Mitsutaka Yamamoto, Martina Schinke-Braun, Jeffrey A. Brown, Bin Tian, Junichi Sadoshima

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Thioredoxin1 (Trx1) inhibits hypertrophy and exhibits protective functions in the heart. To elucidate further the cardiac functions of Trx1, we used a DNA microarray analysis, with hearts from transgenic mice with cardiac-specific overexpression of Trx1 (Tg-Trx1, n = 4) and nontransgenic controls (n = 4). Expression of a large number of genes is regulated in Tg-Trx1, with a greater number of genes downregulated, versus upregulated, at high-fold changes. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene was among the top 50 significantly upregulated genes. By pathway analyses, we found that genes involved in both mitochondrial oxidative phosphorylation and the TCA cycle were upregulated in Tg-Trx1. We confirmed up-regulation of cytochrome c oxidase (COX) components and mitochondrial transcription factor A in Tg-Trx1. The activity of citrate synthase and COX and the cardiac ATP content were significantly higher in Tg-Trx1. A transcription factor binding-site analysis showed that upregulated genes frequently contained binding sites for nuclear respiratory factor 1 (NRF1). Expression of NRF1 and PGC-1α was upregulated in Tg-Trx1, and Trx1 stimulated the transcriptional activity of NRF1 and NRF2 in cardiac myocytes. These results suggest that, in cardiac myocytes, Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions, possibly through PGC-1α and NRFs.

Original languageEnglish
Pages (from-to)1635-1649
Number of pages15
JournalAntioxidants and Redox Signaling
Volume8
Issue number9-10
DOIs
Publication statusPublished - Sep 1 2006

Fingerprint

Mitochondrial Proteins
Oxidative Phosphorylation
Nuclear Respiratory Factor 1
Up-Regulation
Genes
Cardiac Myocytes
Binding Sites
Citrate (si)-Synthase
Peroxisome Proliferator-Activated Receptors
Electron Transport Complex IV
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Hypertrophy
Transgenic Mice
Oxidoreductases
Transcription Factors
Down-Regulation
Adenosine Triphosphate
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart. / Ago, Tetsuro; Yeh, Ijen; Yamamoto, Mitsutaka; Schinke-Braun, Martina; Brown, Jeffrey A.; Tian, Bin; Sadoshima, Junichi.

In: Antioxidants and Redox Signaling, Vol. 8, No. 9-10, 01.09.2006, p. 1635-1649.

Research output: Contribution to journalArticle

Ago, Tetsuro ; Yeh, Ijen ; Yamamoto, Mitsutaka ; Schinke-Braun, Martina ; Brown, Jeffrey A. ; Tian, Bin ; Sadoshima, Junichi. / Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart. In: Antioxidants and Redox Signaling. 2006 ; Vol. 8, No. 9-10. pp. 1635-1649.
@article{fa208190088b4e99906b0592030aef00,
title = "Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart",
abstract = "Thioredoxin1 (Trx1) inhibits hypertrophy and exhibits protective functions in the heart. To elucidate further the cardiac functions of Trx1, we used a DNA microarray analysis, with hearts from transgenic mice with cardiac-specific overexpression of Trx1 (Tg-Trx1, n = 4) and nontransgenic controls (n = 4). Expression of a large number of genes is regulated in Tg-Trx1, with a greater number of genes downregulated, versus upregulated, at high-fold changes. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene was among the top 50 significantly upregulated genes. By pathway analyses, we found that genes involved in both mitochondrial oxidative phosphorylation and the TCA cycle were upregulated in Tg-Trx1. We confirmed up-regulation of cytochrome c oxidase (COX) components and mitochondrial transcription factor A in Tg-Trx1. The activity of citrate synthase and COX and the cardiac ATP content were significantly higher in Tg-Trx1. A transcription factor binding-site analysis showed that upregulated genes frequently contained binding sites for nuclear respiratory factor 1 (NRF1). Expression of NRF1 and PGC-1α was upregulated in Tg-Trx1, and Trx1 stimulated the transcriptional activity of NRF1 and NRF2 in cardiac myocytes. These results suggest that, in cardiac myocytes, Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions, possibly through PGC-1α and NRFs.",
author = "Tetsuro Ago and Ijen Yeh and Mitsutaka Yamamoto and Martina Schinke-Braun and Brown, {Jeffrey A.} and Bin Tian and Junichi Sadoshima",
year = "2006",
month = "9",
day = "1",
doi = "10.1089/ars.2006.8.1635",
language = "English",
volume = "8",
pages = "1635--1649",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "9-10",

}

TY - JOUR

T1 - Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart

AU - Ago, Tetsuro

AU - Yeh, Ijen

AU - Yamamoto, Mitsutaka

AU - Schinke-Braun, Martina

AU - Brown, Jeffrey A.

AU - Tian, Bin

AU - Sadoshima, Junichi

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Thioredoxin1 (Trx1) inhibits hypertrophy and exhibits protective functions in the heart. To elucidate further the cardiac functions of Trx1, we used a DNA microarray analysis, with hearts from transgenic mice with cardiac-specific overexpression of Trx1 (Tg-Trx1, n = 4) and nontransgenic controls (n = 4). Expression of a large number of genes is regulated in Tg-Trx1, with a greater number of genes downregulated, versus upregulated, at high-fold changes. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene was among the top 50 significantly upregulated genes. By pathway analyses, we found that genes involved in both mitochondrial oxidative phosphorylation and the TCA cycle were upregulated in Tg-Trx1. We confirmed up-regulation of cytochrome c oxidase (COX) components and mitochondrial transcription factor A in Tg-Trx1. The activity of citrate synthase and COX and the cardiac ATP content were significantly higher in Tg-Trx1. A transcription factor binding-site analysis showed that upregulated genes frequently contained binding sites for nuclear respiratory factor 1 (NRF1). Expression of NRF1 and PGC-1α was upregulated in Tg-Trx1, and Trx1 stimulated the transcriptional activity of NRF1 and NRF2 in cardiac myocytes. These results suggest that, in cardiac myocytes, Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions, possibly through PGC-1α and NRFs.

AB - Thioredoxin1 (Trx1) inhibits hypertrophy and exhibits protective functions in the heart. To elucidate further the cardiac functions of Trx1, we used a DNA microarray analysis, with hearts from transgenic mice with cardiac-specific overexpression of Trx1 (Tg-Trx1, n = 4) and nontransgenic controls (n = 4). Expression of a large number of genes is regulated in Tg-Trx1, with a greater number of genes downregulated, versus upregulated, at high-fold changes. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene was among the top 50 significantly upregulated genes. By pathway analyses, we found that genes involved in both mitochondrial oxidative phosphorylation and the TCA cycle were upregulated in Tg-Trx1. We confirmed up-regulation of cytochrome c oxidase (COX) components and mitochondrial transcription factor A in Tg-Trx1. The activity of citrate synthase and COX and the cardiac ATP content were significantly higher in Tg-Trx1. A transcription factor binding-site analysis showed that upregulated genes frequently contained binding sites for nuclear respiratory factor 1 (NRF1). Expression of NRF1 and PGC-1α was upregulated in Tg-Trx1, and Trx1 stimulated the transcriptional activity of NRF1 and NRF2 in cardiac myocytes. These results suggest that, in cardiac myocytes, Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions, possibly through PGC-1α and NRFs.

UR - http://www.scopus.com/inward/record.url?scp=33750405658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750405658&partnerID=8YFLogxK

U2 - 10.1089/ars.2006.8.1635

DO - 10.1089/ars.2006.8.1635

M3 - Article

C2 - 16987018

AN - SCOPUS:33750405658

VL - 8

SP - 1635

EP - 1649

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 9-10

ER -