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 P. Singh, Dhirendra P. Singh

Research output: Contribution to journalArticle

81 Scopus citations

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 (US)
Pages (from-to)C842-C855
JournalAmerican Journal of Physiology - Cell Physiology
Volume294
Issue number3
DOIs
StatePublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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