Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy
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 w...
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2024-02-01
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author | Jingchun Bai Xinyu Wang Yiqiu Chen Qiongyu Yuan Zhaoyu Yang Yuling Mi Caiqiao Zhang |
author_facet | Jingchun Bai Xinyu Wang Yiqiu Chen Qiongyu Yuan Zhaoyu Yang Yuling Mi Caiqiao Zhang |
author_sort | Jingchun Bai |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-5ace61c882e84908841aa57b8b9494002024-03-12T16:41:38ZengMDPI AGCells2073-44092024-02-0113541510.3390/cells13050415Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting AutophagyJingchun Bai0Xinyu Wang1Yiqiu Chen2Qiongyu Yuan3Zhaoyu Yang4Yuling Mi5Caiqiao Zhang6College of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, ChinaWith 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.https://www.mdpi.com/2073-4409/13/5/415nobiletinoxidative stressmitophagyovarian agingchicken |
spellingShingle | Jingchun Bai Xinyu Wang Yiqiu Chen Qiongyu Yuan Zhaoyu Yang Yuling Mi Caiqiao Zhang Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy Cells nobiletin oxidative stress mitophagy ovarian aging chicken |
title | Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy |
title_full | Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy |
title_fullStr | Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy |
title_full_unstemmed | Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy |
title_short | Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy |
title_sort | nobiletin ameliorates aging of chicken ovarian prehierarchical follicles by suppressing oxidative stress and promoting autophagy |
topic | nobiletin oxidative stress mitophagy ovarian aging chicken |
url | https://www.mdpi.com/2073-4409/13/5/415 |
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