Isorhamnetin protects zearalenone-induced damage via the PI3K/Akt signaling pathway in porcine ovarian granulosa cells  

作　　者：Xiaoya Li Huali Chen Zelin Zhang Jiaxin Duan Rongmao Hua Xiaodi Li Li Yang Jianyong Cheng Qingwang Li 

机构地区：[1]College of Animal Science and Technology,Northwest A&F University,Yangling,712100,China [2]School of Life Science and Engineering,Southwest University of Science and Technology,Mianyang 621000,China [3]College of Basic Medicine,Hebei University of Chinese Medicine,Shijiazhuang,050000,China

出　　处：《Animal Nutrition》2022年第4期381-390,共10页动物营养（英文版）

基　　金：financially supported by Ministry of Agriculture Transgenic Major Projects(2018ZX0801013B);Key Industry Innovation Chain of Shaanxi Province(2018ZDCXL-NY-02-06)。

摘　　要：Zearalenone(ZEA)is widely derived from moldy cereal grain,which has adverse effects on animal reproduction.In particular,pigs are more sensitive to ZEA-induced toxicity than other animals.Isorhamnetin has extensive pharmacological activity.However,the role of isorhamnetin in ZEA-induced cytotoxicity remains unclear.This study was designed to investigate the therapeutic effect of isorhamnetin on ZEA-induced damage in porcine ovarian granulosa cells and elucidate its molecular mechanism.Two experiments were conducted,where a minimum of 3 biological replicates were used for each treatment.In Exp.1,ovarian granulosa cells were treated with different concentrations of isorhamnetin(1,5,10,20 and 30μmol/L)and ZEA(0,10,30,60,90 and 120μmol/L)for 24 h.Our results indicated that 60μmol/L ZEA(half-maximal inhibitory concentration value)and 20μmol/L isorhamnetin(the most effective concentration against ZEA-induced cytotoxicity)were optimum concentrations.In Exp.2,ovarian granulosa cells were treated with isorhamnetin(20μmol/L)for 2 h,before treatment with ZEA(60μmol/L)for 24 h.Apoptosis,endoplasmic reticulum stress,oxidative stress,proliferation and hormone secretion of ovarian granulosa cells were detected.Our findings showed that isorhamnetin suppressed(P<0.05)ZEA-induced apoptosis by altering mitochondrial membrane potential and apoptosis-related proteins(B-cell lymphoma-2[Bcl-2],Bcl2-associated x[Bax]and cleaved caspase-3[C-Casp3]).Changes in intracellular Ca2+levels and C/EBP homologous protein(CHOP),recombinant activating transcription factor 6(ATF6),glucose regulated protein78 k D(GRP78)indicated that isorhamnetin rescued(P<0.05)ZEA-induced endoplasmic reticulum stress.Furthermore,isorhamnetin prevented(P<0.05)ZEA-induced oxidative stress via the mitogen-activated protein kinase(P38)signaling pathway.Mechanistically,isorhamnetin stimulated(P<0.05)the expression of proliferating cell nuclear antigen(PCNA)and cyclin D,thereby increasing the ratio of S phase cells in response to ZEAinduced apoptosis via phosphatidy

关 键 词：ZEARALENONE ISORHAMNETIN OVARIAN GRANULOSA cell Apoptosis Endoplasmic reticulum STRESS Oxidative STRESS 

分 类 号：S859.8[农业科学—临床兽医学]