Shioji Keisuke, Nakamura Hajime, Masutani Hiroshi, Yodoi Junji
Department of Cardiovascular Medicine, Graduated School of Medicine, Kyoto University, Kyoto, Japan.
Antioxid Redox Signal. 2003 Dec;5(6):795-802. doi: 10.1089/152308603770380106.
Increasing evidence has indicated that the modulation of intracellular redox states has important aspects to cellular events, such as cellular proliferation, activation, growth inhibition, or death via the regulation of intracellular signal transduction and gene expression. Thioredoxin (TRX) is a multifunctional stress-inducible protein, which protects cells from various types of stresses. TRX has not only a scavenging activity of reactive oxygen species, but also a regulating activity of various intracellular molecules including transcription factors. We demonstrated that the serum TRX levels are correlated with the severity of heart failure, and are negatively correlated with left ventricular ejection fractions of patients with heart failure. The expression of TRX is enhanced in endothelial cells and macrophages in human atherosclerotic plaques, in balloon-injured rat arteries, and in damaged cardiomyocytes of rats with acute myocarditis. Overexpression of TRX in transgenic mice attenuates adriamycin-induced cardiotoxicity by reducing oxidative stresses. These findings suggest that TRX and the redox system modulated by TRX have an important role in cellular defense against oxidative stress in cardiovascular diseases.
越来越多的证据表明，细胞内氧化还原状态的调节对于细胞事件具有重要意义，例如通过调节细胞内信号转导和基因表达来影响细胞增殖、激活、生长抑制或死亡。硫氧还蛋白（TRX）是一种多功能应激诱导蛋白，可保护细胞免受各种类型的应激。TRX不仅具有清除活性氧的能力，还具有调节包括转录因子在内的各种细胞内分子的活性。我们证明，血清TRX水平与心力衰竭的严重程度相关，并且与心力衰竭患者的左心室射血分数呈负相关。在人类动脉粥样硬化斑块的内皮细胞和巨噬细胞、球囊损伤的大鼠动脉以及急性心肌炎大鼠受损的心肌细胞中，TRX的表达增强。在转基因小鼠中过表达TRX可通过降低氧化应激来减轻阿霉素诱导的心脏毒性。这些发现表明，TRX以及由TRX调节的氧化还原系统在心血管疾病中细胞对抗氧化应激的防御中起重要作用。
