Involvement of JNK/FOXO1 pathway in apoptosis induced by severe hypoxia in porcine granulosa cells
Involvement of JNK/FOXO1 pathway in apoptosis induced by severe hypoxia in porcine granulosa cells
复制标题
JNK/FOXO1通路参与严重缺氧诱导的猪颗粒细胞凋亡
DOI：
10.1016/j.theriogenology.2020.05.019
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发表时间：
2020-09-15
期刊：
影响因子：
2.8
通讯作者：
Liu, Honglin
中科院分区：
文献类型：
--
作者：
Liu, Zhaojun;Li, Chengyu;Liu, Honglin
在卵巢中，卵泡在每个发育阶段都经历周期性的退化过程，即闭锁。颗粒细胞（GC）凋亡被认为是滤泡闭锁的标志。颗粒间室内的无血管环境被认为会导致缺氧。缺氧对器官、组织、细胞的影响可以是积极的，也可以是消极的，这取决于缺氧的严重程度和环境。本研究旨在探讨体外条件下严重缺氧是否以及如何影响猪GCs的凋亡。目前的研究结果表明，严重缺氧（1% O-2）下猪GCs的凋亡与c-Jun n -末端激酶（JNK）激活增强、FOXO1核积累、cleaved caspase-3水平升高、BCL-2/BAX比值降低有关。进一步的研究表明，严重缺氧介导的JNK激活是猪GCs凋亡和fox01核转运所必需的。此外，在严重缺氧暴露下，FOXO1的抑制减少了GCs的凋亡。综上所述，这些发现表明严重缺氧可能通过JNK/FOXO1轴诱导猪GCs凋亡。(C) 2020爱思唯尔公司版权所有。
In ovaries, follicles undergo a periodic process of degeneration, namely atresia, during each stage of development. Granulosa cell (GC) apoptosis is believed as the hallmark of follicular atresia. The avascular environment within the granulosa compartment is supposed to cause hypoxic conditions. The effects of hypoxia on organs, tissues, cells can be either positive or negative, depending on the severity and context. The present study aimed to explore whether and how severe hypoxia under in vitro conditions functions in apoptosis of porcine GCs. The current results showed that the apoptosis in porcine GCs exposed to severe hypoxia (1% O-2) was correlated with enhanced activation of c-Jun N-terminal kinase (JNK), nuclear accumulation of FOXO1, as well as elevated level of cleaved caspase-3 and decreased ratio of BCL-2/BAX. Further investigations revealed that severe hypoxia-mediated JNK activation was required for the apoptotic death of porcine GCs and the nuclear transport of FOXO1. Moreover, inhibition of FOXO1 reduced GCs apoptosis upon severe hypoxia exposure. Together, these findings suggested that severe hypoxia might act through JNK/FOXO1 axis to induce apoptosis in porcine GCs. (C) 2020 Elsevier Inc. All rights reserved.