Impaired homeostasis and phenotypic abnormalities in Prdx6-/-mice lens epithelial cells by reactive oxygen species

Increased expression and activation of TGF β

N. Fatma, E. Kubo, P. Sharma, D. R. Beier, Dhirendra P Singh

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

PRDX6, a member of the peroxiredoxins (PRDXs) family, is a key player in the removal of reactive oxygen species (ROS). Using targeted inactivation of the Prdx6 gene, we present evidence that the corresponding protein offsets the deleterious effects of ROS on lens epithelial cells (LECs) and regulates gene expression by limiting its levels. PRDX6-depleted LECs displayed phenotypic alterations and elevated α-smooth muscle actin and βig-h3 expression (markers for cataractogenesis), indistinguishable from transforming growth factor β (TGFβ)-induced changes. Biochemical assays disclosed enhanced levels of ROS, as well as high expression and activation of TGFβ1 in Prdx6-/- LECs. A CAT assay revealed transcriptional repression of lens epithelium-derived growth factor (LEDGF), HSP27, and αB-crystallin promoter activities in these cells. A gel mobility shift assay demonstrated the attenuation of LEDGF binding to heat shock or stress response elements present in these genes. A supply of PRDX6 to Prdx6-/- LECs reversed these changes. Based on the above data, we propose a rheostat role for PRDX6 in regulating gene expression by controlling the ROS level to maintain cellular homeostasis.

Original languageEnglish (US)
Pages (from-to)734-750
Number of pages17
JournalCell Death and Differentiation
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2005

Fingerprint

Transforming Growth Factors
Lenses
Reactive Oxygen Species
Homeostasis
Epithelial Cells
Heat-Shock Response
Peroxiredoxins
Gene Expression
Crystallins
Response Elements
Gene Silencing
Electrophoretic Mobility Shift Assay
Smooth Muscle
Actins
Gels
Genes
Proteins
lens epithelium-derived growth factor

Keywords

  • AOP2
  • Apoptosis
  • LEDGF
  • Oxidative stress
  • PRDX6
  • Phenotypic changes
  • Reactive oxygen species
  • TGGβ

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Impaired homeostasis and phenotypic abnormalities in Prdx6-/-mice lens epithelial cells by reactive oxygen species : Increased expression and activation of TGF β. / Fatma, N.; Kubo, E.; Sharma, P.; Beier, D. R.; Singh, Dhirendra P.

In: Cell Death and Differentiation, Vol. 12, No. 7, 01.07.2005, p. 734-750.

Research output: Contribution to journalArticle

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