Activation of CREBZF Increases Cell Apoptosis in Mouse Ovarian Granulosa Cells by Regulating the ERK1/2 and mTOR Signaling Pathways.
Activation of CREBZF Increases Cell Apoptosis in Mouse Ovarian Granulosa Cells by Regulating the ERK1/2 and mTOR Signaling Pathways.
复制标题
CREBZF 的激活通过调节 ERK1/2 和 mTOR 信号通路增加小鼠卵巢颗粒细胞的细胞凋亡
DOI：
10.3390/ijms19113517
复制
发表时间：
2018-11-08
影响因子：
5.6
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Chen F;Wen X;Lin P;Chen H;Wang A;Jin Y
CREBZF是一种多功能转录调节因子，参与多种细胞功能的调节。本研究旨在检测CREBZF在卵巢中的表达定位，探讨CREBZF在卵巢颗粒细胞凋亡中的作用及其相关机制。免疫组化结果显示，CREBZF在动情周期中主要定位于颗粒细胞和卵母细胞。Western blot分析表明，SMILE是CREBZF在卵巢中的主要亚型。通过CREBZF过表达和敲低来评估细胞凋亡与CREBZF之间的关系。流式细胞仪分析显示CREBZF诱导颗粒细胞凋亡。Western blot分析表明，CREBZF的过表达上调BAX和切割Caspase-3，而它下调BCL-2。此外，CREBZF的过表达通过细胞内调节激酶1/2（ERK 1/2）和p70 S6激酶（S6K1）的磷酸化抑制ERK 1/2和mTOR信号通路。此外，我们发现CREBZF还通过增加LC 3-II激活自噬。总之，这些结果表明CREBZF可能通过调节ERK 1/2和mTOR信号通路在颗粒细胞的细胞凋亡中发挥促凋亡作用。
CREBZF, a multifunction transcriptional regulator, participates in the regulation of numerous cellular functions. The aims of the present study were to detect the localization of CREBZF expression in the ovary and explore the role of CREBZF and related mechanisms in the apoptosis of ovarian granulosa cells. We found by immunohistochemistry that CREBZF was mainly located in granulosa cells and oocytes during the estrous cycle. Western blot analysis showed that SMILE was the main isoform of CREBZF in the ovary. The relationship between apoptosis and CREBZF was assessed via CREBZF overexpression and knockdown. Flow cytometry analysis showed that CREBZF induced cell apoptosis in granulosa cells. Western bolt analysis showed that overexpression of CREBZF upregulated BAX and cleaved Caspase-3, while it downregulated BCL-2. Furthermore, overexpression of CREBZF inhibited the ERK1/2 and mTOR signaling pathways through the phosphorylation of intracellular-regulated kinases 1/2 (ERK1/2) and p70 S6 kinase (S6K1). Moreover, we found that CREBZF also activated autophagy by increasing LC3-II. In summary, these results suggest that CREBZF might play a proapoptotic role in cell apoptosis in granulosa cells, possibly by regulating the ERK1/2 and mTOR signaling pathways.
登录
查看更多内容
影响因子：
4.8
作者：
Kayampilly, Pradeep P.;Menon, K. M. J.
通讯作者：
Menon, K. M. J.
DOI：
10.1016/s1071-5576(00)00099-x
发表时间：
2001-01-01
期刊：
JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION
影响因子：
--
作者：
Nilsson, E;Skinner, MK
通讯作者：
Skinner, MK
影响因子：
4.8
作者：
Donaubauer, Elyse M.;Hunzicker-Dunn, Mary E.
通讯作者：
Hunzicker-Dunn, Mary E.
影响因子：
7.7
作者：
Lee, Ji-Min;Seo, Woo-Young;Choi, Hueng-Sik
通讯作者：
Choi, Hueng-Sik
影响因子：
3.9
作者：
Bodnarchuk, Timothy W.;Napper, Scott;Misra, Vikram
通讯作者：
Misra, Vikram