دورية أكاديمية
أعرض في EDS

Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists.

التفاصيل البيبلوغرافية
العنوان: Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists.
المؤلفون: Wyant GA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Yu W; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Doulamis IP; Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA., Nomoto RS; Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA., Saeed MY; Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA., Duignan T; Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA., McCully JD; Department of Cardiac Surgery, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA., Kaelin WG Jr; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
المصدر: Science (New York, N.Y.) [Science] 2022 Aug 05; Vol. 377 (6606), pp. 621-629. Date of Electronic Publication: 2022 Aug 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
أسماء مطبوعة: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
مواضيع طبية MeSH: Kynurenic Acid*/metabolism , Kynurenic Acid*/pharmacology , Kynurenic Acid*/therapeutic use , Mitochondria, Heart*/drug effects , Mitochondria, Heart*/metabolism , Myocardial Ischemia*/metabolism , Myocardial Ischemia*/prevention & control , Receptors, G-Protein-Coupled*/agonists , Receptors, G-Protein-Coupled*/metabolism, Adenosine Triphosphate/metabolism ; Animals ; Humans ; Mice ; Proteins/metabolism ; Rabbits ; ATPase Inhibitory Protein
مستخلص: Kynurenic acid (KynA) is tissue protective in cardiac, cerebral, renal, and retinal ischemia models, but the mechanism is unknown. KynA can bind to multiple receptors, including the aryl hydrocarbon receptor, the a7 nicotinic acetylcholine receptor (a7nAChR), multiple ionotropic glutamate receptors, and the orphan G protein-coupled receptor GPR35. Here, we show that GPR35 activation was necessary and sufficient for ischemic protection by KynA. When bound by KynA, GPR35 activated G i - and G 12/13 -coupled signaling and trafficked to the outer mitochondria membrane, where it bound, apparantly indirectly, to ATP synthase inhibitory factor subunit 1 (ATPIF1). Activated GPR35, in an ATPIF1-dependent and pertussis toxin-sensitive manner, induced ATP synthase dimerization, which prevented ATP loss upon ischemia. These findings provide a rationale for the development of specific GPR35 agonists for the treatment of ischemic diseases.
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Comment in: Trends Pharmacol Sci. 2022 Nov;43(11):891-893. (PMID: 36195494)
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معلومات مُعتمدة: P50 CA101942 United States CA NCI NIH HHS; R35 CA210068 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute
المشرفين على المادة: 0 (GPR35 protein, human)
0 (GPR35 protein, mouse)
0 (Proteins)
0 (Receptors, G-Protein-Coupled)
8L70Q75FXE (Adenosine Triphosphate)
H030S2S85J (Kynurenic Acid)
تواريخ الأحداث: Date Created: 20220804 Date Completed: 20220808 Latest Revision: 20231213
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC9639781
DOI: 10.1126/science.abm1638
PMID: 35926043
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-9203
DOI:10.1126/science.abm1638