Suppression of thioredoxin-1 induces premature senescence in normal human fibroblasts

Jennifer J. Young, Asmita Patel, Priyamvada Rai

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Thioredoxin (TRX) is a ubiquitous multifunctional thiol protein that is critically involved in maintaining cellular redox homeostasis. Levels of thioredoxin-1 (TRX1), the major isoform of TRX, have been shown to correlate with organismal lifespan and age-associated tissue deterioration. Accordingly, we investigated the direct functional effects of suppressing TRX1 levels on cellular senescence, a phenomenon intimately linked with tissue degeneration and aging. Here we find that suppression of TRX1 expression via shRNA rapidly induces premature senescence in young human skin fibroblasts through upregulation of the p53/p21Cip1/Waf1 and p16INK4a tumor suppressor pathways. Moreover, inhibition of these pathways by introduction of SV40 Large T Antigen prevents TRX1 suppression-induced premature senescence but not susceptibility to oxidative stressors. Thus our results suggest that TRX1 has a role in suppressing senescence in normal cells in addition to its function as a redox-protective protein.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume392
Issue number3
DOIs
StatePublished - Feb 12 2010

Fingerprint

Thioredoxins
Fibroblasts
Oxidation-Reduction
Tissue
Polyomavirus Transforming Antigens
Cell Aging
Viral Tumor Antigens
Sulfhydryl Compounds
Small Interfering RNA
Deterioration
Tumors
Skin
Protein Isoforms
Proteins
Homeostasis
Up-Regulation
Aging of materials

Keywords

  • Antioxidant
  • Cell death
  • Cellular senescence
  • Oxidative stress
  • p16
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Suppression of thioredoxin-1 induces premature senescence in normal human fibroblasts. / Young, Jennifer J.; Patel, Asmita; Rai, Priyamvada.

In: Biochemical and Biophysical Research Communications, Vol. 392, No. 3, 12.02.2010, p. 363-368.

Research output: Contribution to journalArticle

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