ROS-induced autophagy regulates porcine trophectoderm cell apoptosis, proliferation, and differentiation
ROS-induced autophagy regulates porcine trophectoderm cell apoptosis, proliferation, and differentiation
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DOI：
10.1152/ajpcell.00256.2018
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发表时间：
2019-02-01
影响因子：
5.5
通讯作者：
Xu, Jianxiong
中科院分区：
文献类型：
--
作者：
Luo, Zhen;Xu, Xue;Xu, Jianxiong
大量胚胎丢失仍然是养猪生产中的一个严重问题。活性氧(ROS)在胚胎着床和胎盘形成过程中起着重要作用。然而，ROS在围着床期对猪滋养外胚层(PTR)细胞命运的潜在机制尚未被研究。本研究旨在阐明ROS对PTR细胞表型的影响及其在细胞贴壁和分化中的调节作用。结果表明，外源性H_2O_2抑制PTR细胞活力，使细胞周期停滞于S和(12/M)期，增加细胞凋亡率和自噬蛋白轻链3B和柏林-1，而不同浓度的N-乙酰-L-半胱氨酸可逆转上述作用。此外，NAC取消了过氧化氢诱导的自噬通量，抑制了细胞内和线粒体的ROS，并恢复了对线粒体NA和生物发生、细胞附着和分化至关重要的基因的表达。NAC以剂量依赖的方式逆转H_2O_2激活的MAPK和Akt/哺乳动物雷帕霉素通路靶标。此外，药理学和RNA干扰方法的分析表明，自噬调节细胞凋亡以及尾端相关的同源盒2和IL-1β的基因表达。总之，这些结果为ROS诱导的自噬在PTR细胞的凋亡、附着和分化中的作用提供了新的见解，表明了一个有希望的目标，以减少猪在围着床期的胚胎丢失。
Significant embryo loss remains a serious problem in pig production. Reactive oxygen species (ROS) play a critical role in embryonic implantation and placentation. However, the potential mechanism of ROS on porcine trophectoderm (pTr) cell fate during the peri-implantation period has not been investigated. This study aimed to elucidate the effects of ROS on pTr cell phenotypes and the regulatory role in cell attachment and differentiation. Herein, results showed that exogenous H2O2 inhibited pTr cell viability, arrested the cell cycle at S and (12/M phases, and increased cell apoptosis and autophagy protein light chain 3B and Berlin-1, whereas these effects were reversed by different concentrations of N-acetyl-L-cysteine (NAC) posttreatment. In addition, NAC abolished H2O2-induced autophagic flux, inhibited intracellular and mitochondrial ROS, and restored expression of genes important for mitochondrial 1)NA and biogenesis, cell attachment, and differentiation. NAC reversed H2O2-activated MAPK and Akt/mammalian target of rapamycin pathways in dose-dependent manners. Furthermore, analyses with pharmacological and RNA interference approaches suggested that autophagy regulated cell apoptosis and gene expression of caudal-related homeobox 2 and IL-1 beta. Collectively, these results provide new insights into the role of the ROS-induced autophagy in pTr cell apoptosis, attachment, and differentiation, indicating a promising target for decreasing porcine conceptus loss during the peri-implantation period.