| First Author | Shioji K | Year | 2002 |
| Journal | Circulation | Volume | 106 |
| Issue | 11 | Pages | 1403-9 |
| PubMed ID | 12221060 | Mgi Jnum | J:134003 |
| Mgi Id | MGI:3784760 | Doi | 10.1161/01.cir.0000027817.55925.b4 |
| Citation | Shioji K, et al. (2002) Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity. Circulation 106(11):1403-9 |
| abstractText | BACKGROUND: Adriamycin (ADR) is an anticancer drug known to cause severe cardiac toxicity by generating free radicals. We investigated the role of a redox-regulating molecule, thioredoxin-1 (TRX1), in ADR-induced cardiotoxicity. METHODS AND RESULTS: The in vitro study showed that TRX1 was dose-dependently increased concomitant with the formation of hydroxyl radicals in ADR-treated neonatal rat cardiomyocytes. Lactate dehydrogenase-releasing assay showed that treatment with recombinant human TRX1 suppressed cardiomyocyte injury in ADR-treated cardiomyocytes. To examine the biological significance of TRX1 in vivo, we used transgenic mice expressing increased levels of human TRX1 (TRX1-TG mice). Electron microscopy revealed that mitochondria, myofibrils, and other cellular details were much better maintained in ADR-treated TRX1-TG mice than in ADR-treated nontransgenic (WT) mice. The increase in the protein carbonyl content, a marker of cellular protein oxidation, was suppressed in ADR-treated TRX1-TG mice compared with ADR-treated WT mice. The formation of hydroxyl radicals in ADR-treated heart homogenates of TRX1-TG mice was decreased compared with WT mice. For the survival study, all WT mice treated with ADR died within 6 weeks, but 5 of 6 TRX1-TG mice treated with ADR survived >8 weeks. CONCLUSIONS: TRX1 is upregulated by intracellular oxidative stress generated by ADR. TRX1 has a protective role against ADR-induced cardiotoxicity by reducing oxidative stress. |
