Bai Jingchun, Wang Xinyu, Chen Yiqiu, Yuan Qiongyu, Yang Zhaoyu, Mi Yuling, Zhang Caiqiao
College of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, China.
Cells. 2024 Feb 27;13(5):415. doi: 10.3390/cells13050415.
With the increase in the age of laying chickens, the aging of follicles is accelerated, and the reproductive ability is decreased. Increased oxidative stress and mitochondrial malfunction are indispensable causes of ovarian aging. In this study, the physiological condition of prehierarchical small white follicles (SWFs) was compared between D280 high-producing chickens and D580 aging chickens, and the effect of a plant-derived flavonoid nobiletin (Nob), a natural antioxidant, on senescence of SWFs granulosa cells (SWF-GCs) was investigated. The results showed that Nob treatment activated cell autophagy by activating the AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT1) pathways in D-galactose (D-gal)-generated senescent SWF-GCs, restoring the expression of proliferation-related mRNAs and proteins. In addition, the expression of inflammation-related protein NF-κB was significantly enhanced in aging GCs that were induced by D-gal. Nob supplementation significantly increased the antioxidant capacity and decreased the expression of several genes associated with cell apoptosis. Furthermore, Nob promoted activation of PINK1 and Parkin pathways for mitophagy and alleviated mitochondrial edema. Either the AMPK inhibitor dorsomorphin (Compound C) or SIRT1 inhibitor selisistat (EX-527) attenuated the effect of Nob on mitophagy. The protective effect of Nob on natural aging, GC proliferation, and elimination of the beneficial impact on energy regulation of naturally aging ovaries was diminished by inhibition of Nob-mediated autophagy. These data suggest that Nob treatment increases the expression of mitophagy-related proteins (PINK1 and Parkin) via the AMPK/SIRT1 pathways to prevent ovarian aging in the laying chickens.
随着蛋鸡年龄的增长，卵泡老化加速，繁殖能力下降。氧化应激增加和线粒体功能障碍是卵巢老化不可或缺的原因。在本研究中，比较了280日龄高产蛋鸡和580日龄老龄蛋鸡前等级小白卵泡（SWFs）的生理状况，并研究了植物来源的类黄酮诺米林（Nob），一种天然抗氧化剂，对SWFs颗粒细胞（SWF-GCs）衰老的影响。结果表明，Nob处理通过激活D-半乳糖（D-gal）诱导衰老的SWF-GCs中的AMP激活蛋白激酶（AMPK）和沉默调节蛋白1（SIRT1）途径来激活细胞自噬，恢复增殖相关mRNA和蛋白质的表达。此外，D-gal诱导的衰老颗粒细胞中炎症相关蛋白NF-κB的表达显著增强。补充Nob显著提高了抗氧化能力，并降低了与细胞凋亡相关的几个基因的表达。此外，Nob促进了PINK1和Parkin途径的激活以进行线粒体自噬，并减轻了线粒体水肿。AMPK抑制剂多柔比星（Compound C）或SIRT1抑制剂西利司他（EX-527）均减弱了Nob对线粒体自噬的作用。抑制Nob介导的自噬减弱了Nob对自然衰老、颗粒细胞增殖以及对自然衰老卵巢能量调节的有益影响的保护作用。这些数据表明，Nob处理通过AMPK/SIRT1途径增加线粒体自噬相关蛋白（PINK1和Parkin）的表达，以预防蛋鸡的卵巢衰老。
