Sulforaphane Acts Through NFE2L2 to Prevent Hypoxia-Induced Apoptosis in Porcine Granulosa Cells via Activating Antioxidant Defenses and Mitophagy.
Sulforaphane Acts Through NFE2L2 to Prevent Hypoxia-Induced Apoptosis in Porcine Granulosa Cells via Activating Antioxidant Defenses and Mitophagy.
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DOI：
10.1021/acs.jafc.2c01978
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发表时间：
2022-06
影响因子：
6.1
通讯作者：
Xuan Zhang;Yuanyuan Chen;Hongmin Li;Baobao Chen;Zhaojun Liu;Gang Wu;Chengyu Li;Rongyang Li;Yan Cao;Jiaqi Zhou;M. Shen;Honglin Liu;Jingli Tao
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作者：
Xuan Zhang;Yuanyuan Chen;Hongmin Li;Baobao Chen;Zhaojun Liu;Gang Wu;Chengyu Li;Rongyang Li;Yan Cao;Jiaqi Zhou;M. Shen;Honglin Liu;Jingli Tao
在哺乳动物中，绝大多数卵泡发生闭锁，这是由颗粒细胞（GC）凋亡引起的。卵泡中的GC暴露于低氧。缺氧触发活性氧（ROS）产生，这导致细胞氧化应激和凋亡。萝卜硫素（SFN）是一种富含于十字花科蔬菜中的植物化学物质异硫氰酸酯，在缓解氧化应激方面具有重要作用。为探讨SFN对缺氧环境下猪胃癌细胞凋亡的影响，建立了缺氧（1%O2）培养猪胃癌细胞模型。结果表明，SFN挽救了缺氧诱导的GC凋亡和活力。同时，SFN可增加缺氧条件下GC胞浆和线粒体中抗氧化酶的表达，减少ROS的积累。在机制上，SFN激活了氧化还原敏感核因子-红细胞2相关因子2（NFE 2L 2）的转录因子进入细胞核，进一步诱导线粒体自噬，提高抗氧化能力，最终缓解缺氧对猪GCs的不利影响。总之，SFN通过NFE 2L 2激活抗氧化防御和线粒体自噬来抑制缺氧诱发的GC凋亡。这些发现可能为调控卵泡发育和闭锁提供新的靶点。
In mammals, a vast majority of ovarian follicles undergo atresia, which is caused by granulosa cell (GC) apoptosis. GCs in follicles are exposed to low oxygen. Hypoxia triggers reactive oxygen species (ROS) generation, which leads to cell oxidative stress and apoptosis. Sulforaphane (SFN), a phytochemical isothiocyanate enriched in cruciferous vegetables, has exhibited a crucial role in mitigating oxidative stress. To explore the effect of SFN on porcine GC apoptosis in a hypoxic environment, we handled the established hypoxia model (1% O2) of cultured porcine GCs with SFN. Results showed that SFN rescued hypoxia-induced apoptosis and viability of GCs. Meanwhile, SFN increased the expression of antioxidant enzymes and reduced the accumulation of ROS in GC cytoplasm and mitochondria under hypoxia. Mechanically, SFN activated the transcription factor of redox-sensitive nuclear factor-erythroid 2-related factor 2 (NFE2L2) entering the nucleus, further inducing mitophagy and increased antioxidant capacity, finally alleviating the adverse effect of hypoxia on porcine GCs. In conclusion, SFN inhibited hypoxia-evoked GC apoptosis by activating antioxidant defenses and mitophagy through NFE2L2. New targets may be provided for regulating follicular development and atresia by these findings.