UFL1 alleviates ER stress and apoptosis stimulated by LPS via blocking the ferroptosis pathway in human granulosa-like cells
UFL1 alleviates ER stress and apoptosis stimulated by LPS via blocking the ferroptosis pathway in human granulosa-like cells
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UFL1 通过阻断人颗粒样细胞的铁死亡途径减轻内质网应激和 LPS 刺激的细胞凋亡
DOI：
10.1007/s12192-022-01284-y
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
Zezheng Pan
中科院分区：
文献类型：
--
作者：
Jingyi Li;Xiangting Tang;Xueer Tu;Zhe Jin;Hao Dong;Qi Yang;Ting Yao;Zezheng Pan
泛素样修饰物1连接酶1（UFL 1）是UFM化系统中独特的E3连接酶。最近的研究表明，这种酶在内质网应激（ER应激）和细胞凋亡过程中起着至关重要的作用。脂多糖（Lipopolysaccharide，LPS）可通过触发ER应激和凋亡，损伤卵巢颗粒细胞，阻碍卵泡发育。本研究旨在探讨UFL 1减轻LPS诱导的人粒层细胞样细胞（KGN）内质网应激和凋亡的机制。在本研究中，我们发现，在LPS刺激下，KGN中UFL 1的蛋白水平明显增加，并且当UFL 1被敲低时，ER应激和凋亡进一步加重;相反，当UFL 1过表达时，这些事件被挽救。接下来，我们发现，在抑制UFL 1表达后，亚铁凋亡相关蛋白的水平相对改变，伴随着活性氧（ROS）和Fe 2+的积累。相反，UFL 1的过表达通过调节P53/SLC 7A 11（溶质载体家族7，成员11，SLC 7A 11）系统和响应于LPS刺激的自噬来逆转铁凋亡过程。此外，KGN中的细胞凋亡和ER应激通过施用铁凋亡抑制剂ferrostatin-1（Fer-1）来拯救。总的来说，我们的研究证明了UFL 1可以减轻LPS刺激的ER应激和凋亡的新机制;这是通过调节KGN中的铁凋亡途径发生的，可能为生殖领域的研究提供新的策略。
Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is a unique E3 ligase of the UFMylation system. Recent studies have shown that this enzyme plays a crucial role in the processes of endoplasmic reticulum stress (ER stress) and apoptosis. Lipopolysaccharide (LPS) can cause injury to ovarian granule cells and hinder follicular development by triggering ER stress and apoptosis. Our study aimed to investigate the mechanism by which UFL1 alleviates ER stress and apoptosis caused by LPS in human granulosa-like cells (KGNs). In this study, we found that the protein levels of UFL1 were increased obviously under LPS stimulation in KGNs and that ER stress and apoptosis were further aggravated when UFL1 was knocked down; in contrast, these events were rescued when UFL1 was overexpressed. Next, we showed that the levels of ferroptosis-related proteins were relatively altered, accompanied by the accumulation of reactive oxygen species (ROS) and Fe2+, following the inhibition of UFL1 expression. In contrast, the overexpression of UFL1 reversed the ferroptosis process by regulating the P53/SLC7A11 (solute carrier family 7, member 11, SLC7A11) system and autophagy in response to LPS stimulation. Furthermore, apoptosis and ER stress in KGNs are rescued by the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, our research demonstrated a new mechanism for UFL1 that can alleviate ER stress and apoptosis stimulated by LPS; this occurred via the regulation of the ferroptosis pathway in KGNs and may provide a new strategy for research in the field of reproduction.
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影响因子：
19
作者：
Yang WS;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.6
作者：
Lin M;Li L;Zhang Y;Zheng L;Xu M;Rong R;Zhu T
通讯作者：
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p62-Keap1-NRF2 通路的激活可防止肝细胞癌细胞中的铁死亡。
DOI：
10.1002/hep.28251
发表时间：
2016-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sun X;Ou Z;Chen R;Niu X;Chen D;Kang R;Tang D
通讯作者：
Tang D
肿瘤抑制蛋白 p53 和铁死亡网络
影响因子：
7.4
作者：
Kang R;Kroemer G;Tang D
通讯作者：
Tang D
影响因子：
12.4
作者：
Zhang, M.;Zhu, X.;Li, H.
通讯作者：
Li, H.