Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene  

作　　者：Rong Wang Yun Huang Xiaoruo Gan Chenghao Fu Yuemin Li Ning Chen Hao Xi Huishan Guo Wei Zhang Yuhong Lü Yan Zhang Pin Lü 

机构地区：[1]Cardiovascular Medical Science Center,Department of Cell Biology,Key Laboratory of Neural and Vascular Biology of Ministry of Education,Hebei Medical University,Shijiazhuang 050017,China [2]Eco-environmental Monitoring Center of Hebei Province,Shijiazhuang 050031,China [3]Hebei Food Safety Key Laboratory,Hebei Food Inspection and Research Institute,Shijiazhuang 050091,China

出　　处：《Food Science and Human Wellness》2023年第6期2263-2275,共13页食品科学与人类健康（英文）

基　　金：supported by the National Key Research Project of China(2022YFF1100300);National Natural Science Foundation of China(32272328);Natural Science Foundation of Hebei Province(B2022321001);Major Public Welfare Projects in Henan Province(201300110200);National Key Research Project of Hebei Province(20375502D);National Key Research Project of Hebei Province(H2021206427);University Science and Technology Research Project of Hebei Province(QN2017107);Postdoctoral Research Funds of Hebei Medical University(307050100163759).

摘　　要：Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We confi rmed that B[a]P promoted ROS production in vascular smooth muscle cells(VSMCs)in vitro and in vivo,associated with the nuclear translocation of AhR.It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR.However,from the posttranslational modifi cation level,the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear.Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation,and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs,suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR.Next,siRNAs of O-linked N-acetylglucosamine transferase(OGT),O-GlcNAcase(OGA)and OGA inhibitor PUGNAc were used.SiOGT blocks but siOGA and PUGNAc promote B[a]P-dependent AhR nuclear translocation and oxidative stress.Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR.Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress.Our fi ndings highlight a new perspective for AhR nuclear translocation regulated by the competitive modifi cation between phosphorylation and O-GlcNAcylation.

关 键 词：BENZO[A]PYRENE Vascular smooth muscle cells Aryl hydrocarbon receptor Phosphorylation modification O-GlcNAcylation modification 

分 类 号：TS201.6[轻工技术与工程—食品科学]