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Thioredoxin‐like protein 6 (TXNL6) is an H2O2‐inducible reducing system for methionine sulfoxide reductase A (MsrA) repair of oxidized proteins whose expression increases upon aging in the human lens
Author(s) -
LEE KANTOROW W,
BRENNAN L,
MCGREAL R,
KANTOROW M
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.208.x
Subject(s) - msra , methionine sulfoxide reductase , thioredoxin , oxidative stress , lens (geology) , crystallin , mitochondrion , microbiology and biotechnology , biology , thioredoxin reductase , oxidative phosphorylation , methionine sulfoxide , biochemistry , lens fiber , cytochrome c , methionine , nucleus , amino acid , paleontology
Purpose TXNL6 is a thioredoxin‐like protein and we hypothesized that it could function as a reducing system for MsrA repair of methionine sulfoxide inactivated proteins. We therefore examined the levels of TXNL6 in multiple tissues, its subcellular localizatioin in lens cells, its oxidative‐stress induction in lens cells and its ability to serve as a reducing system for MsrA repair of the two key lens proteins α‐crystallin and cytochrome c (Cyt c). Methods TXNL6 mRNA and protein levels were analyzed in human lens epithelia and fiber, and its protein levels evaluated in aging whole human lenses. TXNL6 was localized in human lens epithelial (HLE) cells. TXNL6 induction was evaluated in HLE cells exposed to H2O2. The ability of TXNL6 to serve as a reducing system for MsrA repair of met‐oxidizedα‐crystallin and Cyt c was evaluated. Results TXNL6 was expressed at both the transcript and protein levels in lens epithelia, lens fiber cells and multiple other human tissues. Interestingly, protein levels of TXNL6 increased with age in human lenses. TXNL6 was localized to the mitochondria and cytosol of lens cells. TXNL6 was highly induced by H2O2‐oxidative stress treatment. TXNL6 served as a reducing system for MsrA repair of α‐crystallin and Cyt c in vitro. Conclusion TXNL6 is expressed by the human lens. Its levels increase in the lens with age and it is induced at high levels upon oxidative stress treatment. Importantly, TXNL6 can act as a reducing system for MsrA repair of critical lens proteins suggesting it plays a critical role in lens repair, defense against oxidative stress and prevention of cataract formation.