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作 者:Ping Zhou Feng Deng Zi Yang Canhui Cao Hongcui Zhao Fenting Liu Ke Zhong Lin Fu Tianliu Peng Di Sun Hui Liu Rong Li Yang Yu
机构地区:[1]Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [2]Key Laboratory of Assisted Reproduction(Peking University),Ministry of Education,Beijing 100191,China [3]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology,Beijing 100191,China [4]National Clinical Research Center for Obstetrics and Gynecology(Peking University Third Hospital),Beijing 100191,China [5]Clinical Stem Cell Research Center,Peking University Third Hospital,Beijing 100191,China
出 处:《Science China(Life Sciences)》2022年第11期2301-2315,共15页中国科学(生命科学英文版)
基 金:the National Natural Science Foundation of China(82101714,81925013,81971381,81771580,81771650,82071612,and 81571400);China Postdoctoral Science Foundation(2021M690259,2021M702223);the National Key Research and Development Project of China(2016YFC1000601,2018YFC1004101)。
摘 要:Ginsenoside Rb1 shows a strong antioxidant effect and has potential activation effects on Akt.The aim of the present study was to investigate the protective effect of Rb1 on age-related ovarian granulosa cell injury.Ovarian granulosa cells(GCs)were obtained from 50 young women(≤30 years)and 50 aged women(≥38 years)at an IVF center.Young and aged ICR mice were administered with or without Rb1(10 mg kg^(-1),i.p.)for 2 weeks.The protective effects of Rb1 were investigated and the role of Rb1 on the modulation of Akt-FoxO1 interaction was determined with immunofluorescence,Western blotting,immunoprecipitation,si RNA silencing and pharmacological inhibitor.Rb1 effectively decreased LDH and MDA,and reversed the apoptotic-related protein levels in h GL cells from old patients.Similar results were found in mice.In addition,the mitochondrial membrane potential was restored and the overaccumulation of ROS was reversed by Rb1.Rb1 preserved peroxide-impaired Akt activation,to some extent,by increasing phosphorylation at Ser473.Rb1 also facilitated p-Akt binding to FoxO1 and promoted the phosphorylation of FoxO1.Si RNA silencing of Akt,Akt inhibitor LY294002,and FoxO1 inhibitor AS1842856 attenuated the effects of Rb1.Ginsenoside Rb1 inhibits age-related GCs oxidative damage by activating Akt phosphorylation at Ser473 and by further interaction with FoxO1.
关 键 词:ginsenoside Rb1 oxidative stress aging granulosa cell AKT FOXO1
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