Protegrin-1 inhibits porcine ovarian granulosa cell apoptosis from H2O2-induced oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro
Protegrin-1 inhibits porcine ovarian granulosa cell apoptosis from H2O2-induced oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro
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DOI：
10.1016/j.theriogenology.2021.11.022
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发表时间：
2021-12-02
期刊：
影响因子：
2.8
通讯作者：
Liu, Canying
中科院分区：
文献类型：
--
作者：
Li, Xuan;Lin, Yufeng;Liu, Canying
在哺乳动物中，氧化应激诱导的颗粒细胞凋亡是卵泡闭锁的主要原因之一，影响卵巢的生理功能。Protegrin-1（PG-1）是一种具有抗菌活性、免疫调节和促生长作用的抗菌肽。PG-1在猪卵巢卵泡中有表达。本研究旨在探讨PG-1对氧化应激诱导的猪卵巢颗粒细胞凋亡的影响及其分子机制。从猪卵泡获得颗粒细胞，用H2O2处理以建立氧化应激模型，然后用或不用PG-1（10 μ g/mL）处理。PG-1显着抑制H2O2诱导的颗粒细胞凋亡后24小时的治疗。此外，这些结果表明，PG-1增加抗凋亡B细胞淋巴瘤/白血病2（BCL 2）的mRNA和蛋白表达以及BCL 2/Bcl-2相关X蛋白（BAX）的比例，同时降低促凋亡BAX和活性caspase-3的表达。Western blot分析发现，PG-1可降低H2O2诱导的RNA样内质网激酶（PERK）和真核起始因子2 α亚基（eIF2 α）的磷酸化水平，以及CCAAT增强子结合蛋白同源蛋白（CHOP）的蛋白表达水平。PERK抑制剂和磷酸化eIF2a抑制剂均能抑制H2O2诱导的颗粒细胞凋亡，并增强PG-1的抗凋亡作用。综上所述，我们的研究结果表明，PG-1抑制猪卵巢颗粒细胞凋亡的氧化应激通过PERK/eIF2 α/CHOP信号通路在体外，这表明新的调节功能的抗菌肽在卵巢。(C)2021年由Elsevier Inc.出版
In mammals, oxidative stress-induced apoptosis of granulosa cells is one of the major causes of follicular atresia, affecting ovarian physiological function. Protegrin-1 (PG-1) is an antimicrobial peptide with effective antimicrobial activity, immunomodulatory function, and porcine growth-promoting effects. PG-1 has been detected in porcine ovaries follicles. This study aimed to investigate the effect of PG-1 on oxidative stress-induced apoptosis of porcine ovarian granulosa cells and the underlying molecular mechanism. Granulosa cells were obtained from porcine follicles and treated with H2O2 to establish the oxidative stress model, and then treated with or without PG-1 (10 mu g/mL). PG-1 significantly suppressed H2O2 -induced apoptosis in granulosa cells after 24 h of treatment. Furthermore, these results revealed that PG-1 increased the mRNA and protein expression of anti-apoptotic B cell lymphoma/leukemia 2 (BCL2) and the BCL2/BcI-2-associated X protein (BAX) ratio while decreasing the expression of proapoptotic BAX and active caspase-3. Using Western blot analysis, it was found that PG-1 decreased the phosphorylation of RNA-like endoplasmic reticulum kinase (PERK) and the alpha-subunit of eukaryotic initiation factor 2 (eIF2 alpha) as well as the protein expression level of CCAAT enhancer-binding protein homologous protein (CHOP), all of which were increased by H2O2. Moreover, inhibitors against PERK and phospho-eIF2a both suppressed the H2O2-induced granulosa cells apoptosis and enhanced the antiapoptosis effect of PG-1. Taken together, our findings demonstrated that PG-1 inhibited porcine ovarian granulosa cell apoptosis from oxidative stress via the PERK/eIF2 alpha/CHOP signaling pathway in vitro, which suggests the novel regulatory function of the antimicrobial peptide in the ovary. (C) 2021 Published by Elsevier Inc.