Nuclear and cytoplasmic peroxlredoxin-1 differentially regulate NF-κB activities

Peroxiredoxins (Prx) are widely distributed and abundant proteins, which control peroxide concentrations and related signaling mechanisms. Prx I is found in the cytoplasm and nucleus, but little is known about compartmentalized Prx1 unction during redox signaling and oxidative stress. We targeted expression vectors to increase Prx1 in nuclei (NLS-Prx1 and cytoplasm (NES-Prx1) in HeLa cells. Results showed that NES-Prx1 inhibited NF-KB activation and nuclear translocation. In contrast, increased NLS-Prx1 did not affect NF-KB nuclear translocation but increased activity of a NF-KB reporter. Both NLS-Prx1 and NES-Prx1 inhibited NF-KB p50 oxidation, suggesting that oxidation of the redox-sensitive cysteine in p50's DNA-binding domain is regulated via peroxide metabolism in both compartments. Interestingly, following treatment with H2O2, nuclear thioredoxin-1 (Trx1) redox status was protected by NLS-Prxl, and cytoplasmic Trx1 was protected by NES-Prx1. Compartmental differences from increasing Prx1 show that the redox poise of cytoplasmic and nuclear thiol systems can be dynamically controlled through peroxide elimination. Such spatial resolution and protein-specific redox. differences imply that the balance of peroxide generation/metabolism in microcompartments provides an important specific component of redox signaling. (C) 2007 Elsevier Inc. All rights reserved.