Selenium supplementation of lung epithelial cells enhances nuclear factor E2-related factor 2 (Nrf2) activation following thioredoxin reductase inhibition

摘要

The trace element selenium (Se) contributes to redox signaling, antioxidant defense, and immune responses in critically ill neonatal and adult patients. Se is required for the synthesis and function of selenoenzymes including thioredoxin (Trx) reductase-1 (TXNRD1) and glutathione peroxidases (GPx). We have previously identified TXNRD1, primarily expressed by airway epithelia, as a promising therapeutic target to prevent lung injury, likely via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. The present studies utilized the TXNRD1 inhibitor auranofin (AFN) to test the hypothesis that Se positively influences Nrf2 activation and selenoenzyme responses in lung epithelial cells. Murine transformed Club cells (mtCCs) were supplemented with 0, 10, 25, or 100?nM Na₂SeO₃ to create a range of Se conditions and were cultured in the presence or absence of 0.5?μM AFN. TXNRD1 and GPX2 protein expression and enzymatic activity were significantly greater upon Se supplementation (p?2SeO₃ when compared to non-supplemented controls (p.