دورية أكاديمية
أعرض في EDS

20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (G q ) to Affect Vascular Function and Trigger Hypertension.

التفاصيل البيبلوغرافية
العنوان: 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (G q ) to Affect Vascular Function and Trigger Hypertension.
المؤلفون: Garcia V; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Gilani A; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Shkolnik B; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Pandey V; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Zhang FF; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Dakarapu R; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Gandham SK; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Reddy NR; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Graves JP; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Gruzdev A; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Zeldin DC; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Capdevila JH; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Falck JR; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.)., Schwartzman ML; From the Department of Pharmacology, New York Medical College School of Medicine, Valhalla (V.G., A.G., B.S., V.P., F.F.Z., M.L.S.); Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas (R.D., S.K.G., N.R.R., J.R.F.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (J.P.G., A.G., D.C.Z.); and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.H.C.). Michal_schwartzman@nymc.edu.
المصدر: Circulation research [Circ Res] 2017 May 26; Vol. 120 (11), pp. 1776-1788. Date of Electronic Publication: 2017 Mar 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
مواضيع طبية MeSH: Endothelium, Vascular/*physiology , Hydroxyeicosatetraenoic Acids/*metabolism , Hypertension/*metabolism , Receptors, G-Protein-Coupled/*metabolism , Signal Transduction/*physiology , Vascular Remodeling/*physiology, Animals ; Cells, Cultured ; Endothelium, Vascular/drug effects ; Humans ; Hydroxyeicosatetraenoic Acids/pharmacology ; Hydroxyeicosatetraenoic Acids/toxicity ; Hypertension/chemically induced ; Male ; Mice ; Mice, Transgenic ; Protein Binding/physiology ; Rats ; Signal Transduction/drug effects ; Vascular Remodeling/drug effects
مستخلص: Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases.
Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists. The present study was undertaken to identify a receptor to which 20-HETE binds and through which it activates a signaling cascade that culminates in many of the functional outcomes attributed to 20-HETE in vitro and in vivo.
Methods and Results: Using crosslinking analogs, click chemistry, binding assays, and functional assays, we identified G-protein receptor 75 (GPR75), currently an orphan G-protein-coupled receptor (GPCR), as a specific target of 20-HETE. In cultured human endothelial cells, 20-HETE binding to GPR75 stimulated Gα q/11 protein dissociation and increased inositol phosphate accumulation and GPCR-kinase interacting protein-1-GPR75 binding, which further facilitated the c-Src-mediated transactivation of epidermal growth factor receptor. This results in downstream signaling pathways that induce angiotensin-converting enzyme expression and endothelial dysfunction. Knockdown of GPR75 or GPCR-kinase interacting protein-1 prevented 20-HETE-mediated endothelial growth factor receptor phosphorylation and angiotensin-converting enzyme induction. In vascular smooth muscle cells, GPR75-20-HETE pairing is associated with Gα q/11 - and GPCR-kinase interacting protein-1-mediated protein kinase C-stimulated phosphorylation of MaxiKβ, linking GPR75 activation to 20-HETE-mediated vasoconstriction. GPR75 knockdown in a mouse model of 20-HETE-dependent hypertension prevented blood pressure elevation and 20-HETE-mediated increases in angiotensin-converting enzyme expression, endothelial dysfunction, smooth muscle contractility, and vascular remodeling.
Conclusions: This is the first report to identify a GPCR target for an eicosanoid of this class. The discovery of 20-HETE-GPR75 pairing presented here provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases.
(© 2017 American Heart Association, Inc.)
التعليقات: Comment in: Circ Res. 2017 May 26;120(11):1696-1698. (PMID: 28546348)
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معلومات مُعتمدة: P01 DK038226 United States DK NIDDK NIH HHS; P01 HL034300 United States HL NHLBI NIH HHS; Z01 ES025034 United States ImNIH Intramural NIH HHS
فهرسة مساهمة: Keywords: cardiovascular diseases; cytochrome P-450 enzyme system; hypertension; receptor, epidermal growth factor; vascular remodeling
المشرفين على المادة: 0 (GPR75 protein, human)
0 (Hydroxyeicosatetraenoic Acids)
0 (Receptors, G-Protein-Coupled)
79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
تواريخ الأحداث: Date Created: 20170323 Date Completed: 20170818 Latest Revision: 20210109
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5446268
DOI: 10.1161/CIRCRESAHA.116.310525
PMID: 28325781
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4571
DOI:10.1161/CIRCRESAHA.116.310525