TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity

Eri Kubo, Nigar Fatma, Yoshio Akagi, David R. Beier, Sanjay Singh, Dhirendra P. Singh

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

A diminished level of endogenous antioxidant in cells/tissues is associated with reduced resistance to oxidative stress. Peroxiredoxin 6 (PRDX6), a protective molecule, regulates gene expression/function by controlling reactive oxygen species (ROS) levels. Using PRDX6 protein linked to TAT, the transduction domain from human immunodeficiency virus type 1 TAT protein, we demonstrated that PRDX6 was transduced into lens epithelial cells derived from rat or mouse lenses. The protein was biologically active, negatively regulating apoptosis and delaying progression of cataractogenesis by attenuating deleterious signaling. Lens epithelial cells from cataractous lenses bore elevated levels of ROS and were susceptible to oxidative stress. These cells harbored increased levels of active transforming growth factor (TGF)-β1 and of α-smooth muscle actin and βig-h3, markers for cataractogenesis. Importantly, cataractous lenses showed a 10-fold reduction in PRDX6 expression, whereas TGF-β1 mRNA and protein levels were elevated. The changes were reversed, and cataractogenesis was delayed when PRDX6 was supplied. Results suggest that delivery of PRDX6 can postpone cataractogenesis, and this should be an effective approach to delaying cataracts and other degenerative diseases that are associated with increased ROS.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume294
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Peroxiredoxin VI
Crystalline Lens
Opacity
Cell death
Cataract
Lenses
Cell Death
Epithelial Cells
Reactive Oxygen Species
Proteins
Oxidative stress
Transforming Growth Factors
Oxidative Stress
Viruses
Gene expression
Smooth Muscle
Muscle
HIV-1
Rats
Actins

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity. / Kubo, Eri; Fatma, Nigar; Akagi, Yoshio; Beier, David R.; Singh, Sanjay; Singh, Dhirendra P.

In: American Journal of Physiology - Cell Physiology, Vol. 294, No. 3, 03.2008.

Research output: Contribution to journalArticle

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AU - Singh, Dhirendra P.

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