Yi-Ming Wang, Hong-Ke Dong, Min Dai, Jing-Xiao Wang, Xiao-Yu Xu, Guo-Qing Zhu, Xiu-Zhen Li
{"title":"去甲肾上腺素通过PKC/ nfκ b介导的NOX2上调促进血管外成纤维细胞的氧化应激。","authors":"Yi-Ming Wang, Hong-Ke Dong, Min Dai, Jing-Xiao Wang, Xiao-Yu Xu, Guo-Qing Zhu, Xiu-Zhen Li","doi":"10.1080/13510002.2025.2494314","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sympathetic overactivity is closely associated with vascular remodeling. Sympathetic fibers dominantly innervate the adventitia of arteries rather than tunica media. Vascular adventitial fibroblasts (VAFs) play crucial roles in vascular remodeling. However, the link between sympathetic overactivity and VAF proliferation and migration is unknown.</p><p><strong>Methods: </strong>Primary VAFs were isolated from the thoracic aorta of spontaneously hypertensive rats and Wistar-Kyoto rats. Norepinephrine (NE) bitartrate monohydrate was applied to VAFs to simulate the sympathetic overactivity.</p><p><strong>Results: </strong>NE increased NADPH oxidase (NOX) 2 expression and superoxide level, which were almost abolished by NOX2 inhibitor GSK2795039 or α-adrenoceptor antagonist prazosin, but not significantly affected by NOX1 inhibitor ML171, NOX4 inhibitor GLX351322 or β-adrenoceptor antagonist propranolol. Superoxide scavenger tempol or NOX2 inhibitor GSK2795039 attenuated NE-induced VAF proliferation and migration. NE promoted protein kinase C (PKC) phosphorylation and NFκB-p65 nuclear translocation. Either PKC inhibitor Go6983 or NFκB inhibitor BAY11-7082 attenuated NE-induced NOX activation, NOX2 upregulation, superoxide production, proliferation and migration.</p><p><strong>Conclusion: </strong>NE promotes oxidative stress by α-receptor/PKC/NFκB-mediated NOX2 upregulation, which contributes to proliferation and migration of VAFs.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2494314"},"PeriodicalIF":7.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024498/pdf/","citationCount":"0","resultStr":"{\"title\":\"Norepinephrine promotes oxidative stress in vascular adventitial fibroblasts via PKC/NFκB-mediated NOX2 upregulation.\",\"authors\":\"Yi-Ming Wang, Hong-Ke Dong, Min Dai, Jing-Xiao Wang, Xiao-Yu Xu, Guo-Qing Zhu, Xiu-Zhen Li\",\"doi\":\"10.1080/13510002.2025.2494314\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Sympathetic overactivity is closely associated with vascular remodeling. Sympathetic fibers dominantly innervate the adventitia of arteries rather than tunica media. Vascular adventitial fibroblasts (VAFs) play crucial roles in vascular remodeling. However, the link between sympathetic overactivity and VAF proliferation and migration is unknown.</p><p><strong>Methods: </strong>Primary VAFs were isolated from the thoracic aorta of spontaneously hypertensive rats and Wistar-Kyoto rats. Norepinephrine (NE) bitartrate monohydrate was applied to VAFs to simulate the sympathetic overactivity.</p><p><strong>Results: </strong>NE increased NADPH oxidase (NOX) 2 expression and superoxide level, which were almost abolished by NOX2 inhibitor GSK2795039 or α-adrenoceptor antagonist prazosin, but not significantly affected by NOX1 inhibitor ML171, NOX4 inhibitor GLX351322 or β-adrenoceptor antagonist propranolol. Superoxide scavenger tempol or NOX2 inhibitor GSK2795039 attenuated NE-induced VAF proliferation and migration. NE promoted protein kinase C (PKC) phosphorylation and NFκB-p65 nuclear translocation. Either PKC inhibitor Go6983 or NFκB inhibitor BAY11-7082 attenuated NE-induced NOX activation, NOX2 upregulation, superoxide production, proliferation and migration.</p><p><strong>Conclusion: </strong>NE promotes oxidative stress by α-receptor/PKC/NFκB-mediated NOX2 upregulation, which contributes to proliferation and migration of VAFs.</p>\",\"PeriodicalId\":21096,\"journal\":{\"name\":\"Redox Report\",\"volume\":\"30 1\",\"pages\":\"2494314\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024498/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Redox Report\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/13510002.2025.2494314\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Report","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/13510002.2025.2494314","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Norepinephrine promotes oxidative stress in vascular adventitial fibroblasts via PKC/NFκB-mediated NOX2 upregulation.
Background: Sympathetic overactivity is closely associated with vascular remodeling. Sympathetic fibers dominantly innervate the adventitia of arteries rather than tunica media. Vascular adventitial fibroblasts (VAFs) play crucial roles in vascular remodeling. However, the link between sympathetic overactivity and VAF proliferation and migration is unknown.
Methods: Primary VAFs were isolated from the thoracic aorta of spontaneously hypertensive rats and Wistar-Kyoto rats. Norepinephrine (NE) bitartrate monohydrate was applied to VAFs to simulate the sympathetic overactivity.
Results: NE increased NADPH oxidase (NOX) 2 expression and superoxide level, which were almost abolished by NOX2 inhibitor GSK2795039 or α-adrenoceptor antagonist prazosin, but not significantly affected by NOX1 inhibitor ML171, NOX4 inhibitor GLX351322 or β-adrenoceptor antagonist propranolol. Superoxide scavenger tempol or NOX2 inhibitor GSK2795039 attenuated NE-induced VAF proliferation and migration. NE promoted protein kinase C (PKC) phosphorylation and NFκB-p65 nuclear translocation. Either PKC inhibitor Go6983 or NFκB inhibitor BAY11-7082 attenuated NE-induced NOX activation, NOX2 upregulation, superoxide production, proliferation and migration.
Conclusion: NE promotes oxidative stress by α-receptor/PKC/NFκB-mediated NOX2 upregulation, which contributes to proliferation and migration of VAFs.
期刊介绍：
Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included.
While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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