{"title":"Epac1和PKA激动剂抑制ROS降低视网膜内皮细胞NLRP3炎性体蛋白。","authors":"Li Liu, Youde Jiang, Jena J Steinle","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Reactive oxygen species (ROS) activate inflammatory pathways in several organs, including the retina. More recent work has shown that ROS activate the NOD-like receptor protein 3 (NLRP3) inflammasome pathway proteins. We recently showed that the exchange protein activated by cAMP 1 (Epac1) and protein kinase A (PKA) regulates NLRP3 proteins in the retina. Our goal was to determine whether Epac1 and PKA reduce ROS and NLRP3 inflammasome proteins.</p><p><strong>Methods: </strong>We used human primary retinal endothelial cells (RECs) grown in normal glucose (5 mM) and stimulated in normal glucose with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to induce ROS and measured NLRP3 pathway proteins. In some groups, we treated cells with an Epac1 or a PKA agonist in addition to H<sub>2</sub>O<sub>2</sub> treatment to determine whether Epac1 and PKA reduced ROS and induced NLRP3 pathway proteins.</p><p><strong>Results: </strong>The data showed that 500 µM H<sub>2</sub>O<sub>2</sub> was the optimal dose to increase ROS in RECs. In RECs treated with H<sub>2</sub>O<sub>2</sub>, NLRP3 pathway proteins were increased, which were significantly reduced by cotreatment with PKA or Epac1 agonists. H<sub>2</sub>O<sub>2</sub> significantly increased NIMA-related kinase 7 (Nek7) and purinergic 2X7 receptor 7 (P2X7) levels, which were blocked by Epac1 and PKA agonists.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that Epac1 and PKA reduce retinal inflammation through the reduced ROS-induced activation of NLRP3 pathway proteins.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/55/mv-v28-500.PMC10115359.pdf","citationCount":"0","resultStr":"{\"title\":\"Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.\",\"authors\":\"Li Liu, Youde Jiang, Jena J Steinle\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Reactive oxygen species (ROS) activate inflammatory pathways in several organs, including the retina. More recent work has shown that ROS activate the NOD-like receptor protein 3 (NLRP3) inflammasome pathway proteins. We recently showed that the exchange protein activated by cAMP 1 (Epac1) and protein kinase A (PKA) regulates NLRP3 proteins in the retina. Our goal was to determine whether Epac1 and PKA reduce ROS and NLRP3 inflammasome proteins.</p><p><strong>Methods: </strong>We used human primary retinal endothelial cells (RECs) grown in normal glucose (5 mM) and stimulated in normal glucose with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to induce ROS and measured NLRP3 pathway proteins. In some groups, we treated cells with an Epac1 or a PKA agonist in addition to H<sub>2</sub>O<sub>2</sub> treatment to determine whether Epac1 and PKA reduced ROS and induced NLRP3 pathway proteins.</p><p><strong>Results: </strong>The data showed that 500 µM H<sub>2</sub>O<sub>2</sub> was the optimal dose to increase ROS in RECs. In RECs treated with H<sub>2</sub>O<sub>2</sub>, NLRP3 pathway proteins were increased, which were significantly reduced by cotreatment with PKA or Epac1 agonists. H<sub>2</sub>O<sub>2</sub> significantly increased NIMA-related kinase 7 (Nek7) and purinergic 2X7 receptor 7 (P2X7) levels, which were blocked by Epac1 and PKA agonists.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that Epac1 and PKA reduce retinal inflammation through the reduced ROS-induced activation of NLRP3 pathway proteins.</p>\",\"PeriodicalId\":18866,\"journal\":{\"name\":\"Molecular Vision\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/55/mv-v28-500.PMC10115359.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Vision\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Vision","FirstCategoryId":"3","ListUrlMain":"","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.
Purpose: Reactive oxygen species (ROS) activate inflammatory pathways in several organs, including the retina. More recent work has shown that ROS activate the NOD-like receptor protein 3 (NLRP3) inflammasome pathway proteins. We recently showed that the exchange protein activated by cAMP 1 (Epac1) and protein kinase A (PKA) regulates NLRP3 proteins in the retina. Our goal was to determine whether Epac1 and PKA reduce ROS and NLRP3 inflammasome proteins.
Methods: We used human primary retinal endothelial cells (RECs) grown in normal glucose (5 mM) and stimulated in normal glucose with hydrogen peroxide (H2O2) to induce ROS and measured NLRP3 pathway proteins. In some groups, we treated cells with an Epac1 or a PKA agonist in addition to H2O2 treatment to determine whether Epac1 and PKA reduced ROS and induced NLRP3 pathway proteins.
Results: The data showed that 500 µM H2O2 was the optimal dose to increase ROS in RECs. In RECs treated with H2O2, NLRP3 pathway proteins were increased, which were significantly reduced by cotreatment with PKA or Epac1 agonists. H2O2 significantly increased NIMA-related kinase 7 (Nek7) and purinergic 2X7 receptor 7 (P2X7) levels, which were blocked by Epac1 and PKA agonists.
Conclusions: Taken together, these data suggest that Epac1 and PKA reduce retinal inflammation through the reduced ROS-induced activation of NLRP3 pathway proteins.
期刊介绍：
Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical).
Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints.
For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.
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