Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene
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 confirmed that B[a]P promoted ROS production in vascular smooth muscle cells...
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| Format: | Article |
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Tsinghua University Press
2023-11-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023000988 |
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| author | Rong Wang Yun Huang Xiaoruo Gan Chenghao Fu Yuemin Li Ning Chen Hao Xi Huishan Guo Wei Zhang Yuhong Lü Yan Zhang Pin Lü |
| author_facet | Rong Wang Yun Huang Xiaoruo Gan Chenghao Fu Yuemin Li Ning Chen Hao Xi Huishan Guo Wei Zhang Yuhong Lü Yan Zhang Pin Lü |
| author_sort | Rong Wang |
| collection | DOAJ |
| description | 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 confirmed 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 modification 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 findings highlight a new perspective for AhR nuclear translocation regulated by the competitive modification between phosphorylation and O-GlcNAcylation. |
| format | Article |
| id | doaj-art-40306b75e6d14888b80abea1e5abce65 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-40306b75e6d14888b80abea1e5abce652025-02-03T03:58:31ZengTsinghua University PressFood Science and Human Wellness2213-45302023-11-0112622632275Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyreneRong Wang0Yun Huang1Xiaoruo Gan2Chenghao Fu3Yuemin Li4Ning Chen5Hao Xi6Huishan Guo7Wei Zhang8Yuhong Lü9Yan Zhang10Pin Lü11Cardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaHebei Food Safety Key Laboratory, Hebei Food Inspection and Research Institute, Shijiazhuang 050091, ChinaCardiovascular Medical Science Center, Department of Cell Biology, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, ChinaEco-environmental Monitoring Center of Hebei Province, Shijiazhuang 050031, China; Corresponding authors.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; Corresponding authors.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 confirmed 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 modification 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 findings highlight a new perspective for AhR nuclear translocation regulated by the competitive modification between phosphorylation and O-GlcNAcylation.http://www.sciencedirect.com/science/article/pii/S2213453023000988Benzo[a]pyreneVascular smooth muscle cellsAryl hydrocarbon receptorPhosphorylation modificationO-GlcNAcylation modification |
| spellingShingle | Rong Wang Yun Huang Xiaoruo Gan Chenghao Fu Yuemin Li Ning Chen Hao Xi Huishan Guo Wei Zhang Yuhong Lü Yan Zhang Pin Lü Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene Food Science and Human Wellness Benzo[a]pyrene Vascular smooth muscle cells Aryl hydrocarbon receptor Phosphorylation modification O-GlcNAcylation modification |
| title | Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene |
| title_full | Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene |
| title_fullStr | Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene |
| title_full_unstemmed | Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene |
| title_short | Switch of phosphorylation to O-GlcNAcylation of AhR contributes to vascular oxidative stress induced by benzo[a]pyrene |
| title_sort | switch of phosphorylation to o glcnacylation of ahr contributes to vascular oxidative stress induced by benzo a pyrene |
| topic | Benzo[a]pyrene Vascular smooth muscle cells Aryl hydrocarbon receptor Phosphorylation modification O-GlcNAcylation modification |
| url | http://www.sciencedirect.com/science/article/pii/S2213453023000988 |
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