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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/C842    most recent 00540.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Kubo, E. Articles by Singh, D. P. Search for Related Content PubMed PubMed Citation Articles by Kubo, E. Articles by Singh, D. P.

GROWTH, DIFFERENTIATION, AND APOPTOSIS

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

¹Department of Ophthalmology, University of Fukui, Fukui, Japan; ²Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska; ³Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and ⁴Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska

Submitted 14 November 2007 ; accepted in final form 7 January 2008

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 -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.

reactive oxygen species; transforming growth factor-β; βig-h3; -smooth muscle actin; oxidative stress

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