title: Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2.
abstract: Reactive oxygen species (ROS) are closely related to the follicular granulosa cell apoptosis. Grape seed procyanidin B2 (GSPB2) has been reported to possess potent antioxidant activity. However, the GSPB2-mediated protective effects and the underlying molecular mechanisms in granulosa cell apoptosis process remain unknown. In this study, we showed for the first time that GSPB2 treatment decreased FoxO1 protein level, improved granulosa cell viability, upregulated LC3-II protein level, and reduced granulosa cell apoptosis rate. Under a condition of oxidative stress, GSPB2 reversed FoxO1 nuclear localization and increased its level in cytoplasm. In addition, FoxO1 knockdown inhibited the protective effects of GSPB2 induced. Our findings suggest that FoxO1 plays a pivotal role in regulating autophagy in granulosa cells, GSPB2 exerts a potent and beneficial role in reducing granulosa cell apoptosis and inducing autophagy process, and targeting FoxO1 could be significant in fighting against oxidative stress-reduced female reproductive system diseases.
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Bin-Wen
authors.initials: BW
authors.lastname: Gao
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Ren
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Zi-Jing
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou 450008, China.
authors.forename: Bao-Song
authors.initials: BS
authors.lastname: Xing
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004178:Diquat / Q000494:pharmacology; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D056604:Grape Seed Extract / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D020011:Protective Agents; D017382:Reactive Oxygen Species; C479580:procyanidin B2; D008315:Malondialdehyde; D002392:Catechin; D004178:Diquat; D006861:Hydrogen Peroxide