Zhang J, Cui X, Wang L, Liu F, Jiang T, Li C, Li D, Huang M, Liao S, Wang J, Chen J, Jia H, He J, Tang Z, Yin Z, Liu M
(M. Liu) College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Rd, Wuhan, Hubei, 430074, P.R. China.
Curr Mol Med. 2014;14(6):772-82. doi: 10.2174/1566524014666140724103927.
Thioredoxins (Trxs) are a class of small molecular redox proteins that play an important role in scavenging abnormally accumulated reactive oxygen species (ROS). Thioredoxin 2 (Trx2) is one member of this family located in mitochondria. Trx2 protects cells from increased oxidative stress and has anti-apoptosis function. Knockout of Trx2 in mice led to early embryonic lethality. However, the essential role of Trx2 during embryogenesis remains unclear. To further investigate the role of Trx2 during embryonic development, we performed Trx2 knockdown in zebrafish and investigated the regulation role of Trx2 during embryonic development. Our results indicate that Trx2 had a high expression in early zebrafish embryos and its knockdown in zebrafish led to defective liver development mainly due to increased hepatic cell death. The increased ROS and the imbalance of members of the Bcl-2 family were involved in cell death induced by Trx2 suppression in zebrafish. The dysregulation of Bax, puma and Bcl-xl promoted the reduction of mitochondrial trans-membrane potential and the mitochondria membrane permeabilization (MMP), which initiated the mitochondrial apoptosis pathway. Additionally, we found that the increase of relocated GAPDH in mitochondria may be another factor responsible for the mitochondrial catastrophe.
硫氧还蛋白（Trxs）是一类小分子氧化还原蛋白，在清除异常积累的活性氧（ROS）方面发挥着重要作用。硫氧还蛋白2（Trx2）是该家族位于线粒体中的一个成员。Trx2保护细胞免受氧化应激增加的影响，并具有抗凋亡功能。在小鼠中敲除Trx2会导致早期胚胎致死。然而，Trx2在胚胎发生过程中的重要作用仍不清楚。为了进一步研究Trx2在胚胎发育中的作用，我们在斑马鱼中进行了Trx2基因敲低，并研究了Trx2在胚胎发育过程中的调控作用。我们的结果表明，Trx2在斑马鱼早期胚胎中高表达，其在斑马鱼中的敲低导致肝脏发育缺陷，主要原因是肝细胞死亡增加。ROS增加以及Bcl-2家族成员失衡参与了斑马鱼中Trx2抑制诱导的细胞死亡。Bax、puma和Bcl-xl的失调促进了线粒体跨膜电位的降低和线粒体膜通透性转换（MMP），从而启动了线粒体凋亡途径。此外，我们发现线粒体中重新定位的甘油醛-3-磷酸脱氢酶（GAPDH）增加可能是导致线粒体灾难的另一个因素。
