| First Author | Go YM | Year | 2013 |
| Journal | Toxicol Sci | Volume | 131 |
| Issue | 1 | Pages | 84-94 |
| PubMed ID | 22961094 | Mgi Jnum | J:192762 |
| Mgi Id | MGI:5466452 | Doi | 10.1093/toxsci/kfs271 |
| Citation | Go YM, et al. (2013) Increased nuclear thioredoxin-1 potentiates cadmium-induced cytotoxicity. Toxicol Sci 131(1):84-94 |
| abstractText | Cadmium (Cd) is a widely dispersed environmental agent that causes oxidative toxicity through mechanisms that are sensitive to thioredoxin-1 (Trx1). Trx1 is a cytoplasmic protein that translocates to nuclei during oxidative stress. Recent research shows that interaction of Trx1 with actin plays a critical role in cell survival and that increased nuclear Trx-1 potentiates proinflammatory signaling and death in cell and mouse models. These observations indicate that oxidative toxicity caused by low-dose Cd could involve disruption of actin-Trx1 interaction, nuclear Trx1 translocation, and potentiation of proinflammatory cell death mechanisms. In this study, we investigated the role of nuclei-localized Trx1 in Cd-induced inflammation and cytotoxicity using in vitro and in vivo models. The results show that Cd stimulated nuclear translocation of Trx1 and p65 of NF-kappaB. Elevation of Trx1 in nuclei in in vitro cells and kidney of transgenic mice potentiated Cd-stimulated NF-kappaB activation and cell death. Cd-stimulated Trx1 nuclear translocation and NF-kappaB activation were inhibited by cytochalasin D, an inhibitor of actin polymerization, suggesting that actin regulates Trx1 nuclear translocation and NF-kappaB activation by Cd. A nuclear-targeted dominant negative form of Trx1 blocked Cd-stimulated NF-kappaB activation and decreased cell death. Addition of zinc, known to antagonize Cd toxicity by increasing metallothionein, had no effect on Cd-stimulated nuclear translocation of Trx1 and NF-kappaB activation. Taken together, the results show that nuclear translocation and accumulation of redox-active Trx1 in nuclei play an important role in Cd-induced inflammation and cell death. |
