{"id":3224,"date":"2023-11-06T12:14:44","date_gmt":"2023-11-06T11:14:44","guid":{"rendered":"http:\/\/www.ub.edu\/ibub\/?p=3224"},"modified":"2023-11-14T14:55:27","modified_gmt":"2023-11-14T13:55:27","slug":"new-strategy-studied-to-reduce-endoplasmic-reticulum-stress-and-inflammation-in-liver-cells","status":"publish","type":"post","link":"https:\/\/www.ub.edu\/ibub\/new-strategy-studied-to-reduce-endoplasmic-reticulum-stress-and-inflammation-in-liver-cells\/","title":{"rendered":"New strategy studied to reduce endoplasmic reticulum stress and inflammation in liver cells"},"content":{"rendered":"\n<p>A new\nstudy, led by the Department of Pharmacology, Toxicology and Therapeutic\nChemistry of the University of Barcelona, the Institute of Biomedicine of the\nUniversity of Barcelona (IBUB) and CIBERDEM, describes the effects of a\ncompound PROTAC (<em>Proteolysis-targeting\nChimera<\/em>) directed against soluble epoxide hydrolase (sEH). This compound,\nby stimulating the degradation of sEH, causes the activation of the metabolic\nsensor AMPK, key in energy balance, thus reducing endoplasmic reticulum stress\nand inflammation in liver cells.&nbsp; <\/p>\n\n\n\n<p>The work, published in the journal Biomedicine &amp; Pharmacotherapy, has been coordinated by professor Manuel V\u00e1zquez Carrera, from the aforementioned Department of the Faculty of Pharmacy and Food Sciences, and has had the participation of two other groups from the IBUB led by UB professors Santiago V\u00e1zquez and Carles Galdeano, in addition to the CIBERDEM group led by expert \u00c1ngela Valverde at the Alberto Sols Institute (UAM-CSIC) and a group from the University of California (United States).<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter is-resized\"><img fetchpriority=\"high\" decoding=\"async\" src=\"https:\/\/www.ub.edu\/ibub\/wp-content\/uploads\/2023\/11\/2023-Not\u00edcia-Manel-V\u00e1zquez.png\" alt=\"\" class=\"wp-image-3225\" width=\"312\" height=\"402\" srcset=\"https:\/\/www.ub.edu\/ibub\/wp-content\/uploads\/2023\/11\/2023-Not\u00edcia-Manel-V\u00e1zquez.png 464w, https:\/\/www.ub.edu\/ibub\/wp-content\/uploads\/2023\/11\/2023-Not\u00edcia-Manel-V\u00e1zquez-233x300.png 233w\" sizes=\"(max-width: 312px) 100vw, 312px\" \/><figcaption> <br>Image of the research team of the Faculty of Pharmacy and Food Sciences, IBUB and CIBERDEM <\/figcaption><\/figure><\/div>\n\n\n\n<p>&#8220;In\nthis study we describe a novel PROTAC directed against the sEH enzyme that\npromotes its degradation in liver cells. The reduction of sEH levels decreases\nmarkers of endoplasmic reticulum stress, a process that chronically sustained\npromotes the development of numerous pathologies such as type 2 diabetes\nmellitus, as well as markers of inflammation in liver cells,&#8221; explains Dr.\nV\u00e1zquez Carrera. The researcher adds that &#8220;these changes are due to an\nactivation by PROTAC of AMPK kinase, which is a pharmacological target for the\ntreatment of insulin resistance and type 2 diabetes&#8221;.<\/p>\n\n\n\n<p>The study\nfurther observed that the reduction in sEH was accompanied by an increase in\nproteins involved in the insulin signaling pathway.<\/p>\n\n\n\n<p>&#8220;While\nthe hydrolase activity of the bifunctional enzyme sEH has been extensively\nstudied and inhibitors are already in clinical trials (for pain, lung disease,\ninsulin resistance, etc.), the phosphatase activity of sEH has been little\nstudied,&#8221; the researcher notes.<\/p>\n\n\n\n<p>Recent\nstudies indicate that inactivating phosphatase activity reduces obesity and\nheart damage. Thus, this work took as its starting point the hypothesis that\nreducing both sEH hydrolase and phosphatase activity may be more beneficial\nthan solely reducing the former.<\/p>\n\n\n\n<p>&#8220;One possible strategy to inhibit both activities is the use of PROTACs, bifunctional compounds that contain an inhibitor of a specific protein, in this case sEH, and which is linked by a linker to a ligand of E3 ligase,&#8221; explains Dr. V\u00e1zquez Carrera. These compounds, in addition to inhibiting the activity of sEH, also stimulate its degradation in the proteasome, thanks to their binding to E3 ligase. Additionally, this new strategy allows the use of smaller doses of compounds and provides an additional layer of selectivity.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><strong>Article reference<\/strong>:<\/p>\n\n\n\n<p>Peyman, Mona; Barroso, Emma; Turcu, Andreea; Estrany, Francesc; Smith, D\u00e1ire; Jurado Aguilar, Javier; Rada, Patricia; Morisseau, Christophe; Hammock, Bruce; Valverde, \u00c1ngela; Palomer, Xavier; Galdeano, Carles; V\u00e1zquez, Santiago; V\u00e1zquez-Carrera, Manuel. Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress. <em>Biomed Pharmacother<\/em> (2023). DOI: <a href=\"https:\/\/doi.org\/10.1016\/j.biopha.2023.115667\">10.1016\/j.biopha.2023.115667<\/a><\/p>\n\n\n\n<p>CIBER News <a href=\"https:\/\/www.ciberdem.org\/noticias\/estudian-una-nueva-estrategia-para-reducir-el-estres-del-reticulo-endoplasmico-y-la-inflamacion-de-las-celulas-hepaticas\">[+]<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A new study, led by the Department of Pharmacology, Toxicology and Therapeutic Chemistry of the University of Barcelona, the Institute of Biomedicine of the University of Barcelona (IBUB) and CIBERDEM, describes the effects of a compound PROTAC (Proteolysis-targeting Chimera) directed against soluble epoxide hydrolase (sEH). This compound, by stimulating the degradation of sEH, causes the &#8230; <a title=\"New strategy studied to reduce endoplasmic reticulum stress and inflammation in liver cells\" class=\"read-more\" href=\"https:\/\/www.ub.edu\/ibub\/new-strategy-studied-to-reduce-endoplasmic-reticulum-stress-and-inflammation-in-liver-cells\/\" aria-label=\"More on New strategy studied to reduce endoplasmic reticulum stress and inflammation in liver cells\">Read more<\/a><\/p>\n","protected":false},"author":2,"featured_media":3237,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-3224","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.5 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>New strategy studied to reduce endoplasmic reticulum stress and inflammation in liver cells - IBUB - Institut de Biomedicina de la Universitat de Barcelona<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ub.edu\/ibub\/new-strategy-studied-to-reduce-endoplasmic-reticulum-stress-and-inflammation-in-liver-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New strategy studied to reduce endoplasmic reticulum stress and inflammation in liver cells - IBUB - Institut de Biomedicina de la Universitat de Barcelona\" \/>\n<meta property=\"og:description\" content=\"A new study, led by the Department of Pharmacology, Toxicology and Therapeutic Chemistry of the University of Barcelona, the Institute of Biomedicine of the University of Barcelona (IBUB) and CIBERDEM, describes the effects of a compound PROTAC (Proteolysis-targeting Chimera) directed against soluble epoxide hydrolase (sEH). This compound, by stimulating the degradation of sEH, causes the ... 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