{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:36:31Z","timestamp":1788233791397,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00034"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00034"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["EFOP-3.6.2-16-2017-00006 (LIVE LONGER)"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00006 (LIVE LONGER)"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["20391-3\/2018\/FEKUSTRAT"],"award-info":[{"award-number":["20391-3\/2018\/FEKUSTRAT"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["OTKA-NKFIH 715 (FK138992),"],"award-info":[{"award-number":["OTKA-NKFIH 715 (FK138992),"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["OTKA-NKFIH (K143889)"],"award-info":[{"award-number":["OTKA-NKFIH (K143889)"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["OTKA-NKFIH (K142371)"],"award-info":[{"award-number":["OTKA-NKFIH (K142371)"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015763","name":"University of Szeged","doi-asserted-by":"publisher","award":["SZTE SZAOK - 720 KKASZGYA2023\/5S775"],"award-info":[{"award-number":["SZTE SZAOK - 720 KKASZGYA2023\/5S775"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005881","name":"Ministry of Human Capacities","doi-asserted-by":"publisher","award":["\u00daNKP-22-5-SZTE-562"],"award-info":[{"award-number":["\u00daNKP-22-5-SZTE-562"]}],"id":[{"id":"10.13039\/501100005881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["BO\/00574\/22"],"award-info":[{"award-number":["BO\/00574\/22"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute myocardial infarction, often associated with ischemia\/reperfusion injury (I\/R), is a major healthcare issue ranking among the leading causes of death globally. Although kynurenic acid (KYNA), an endogenous tryptophan metabolite, has been previously shown to protect the cardiac tissue against I\/R injury, its mechanism of action remains unclear. Therefore, here, we examined whether KYNA administration rescues H9c2 cardiac cells exposed to I\/R through the preservation of the structural and functional integrity of the mitochondria. In addition, we assessed whether KYNA-derived agonism on G-protein coupled receptor 35 (GPR35) is involved in the protection of cardiac cells against simulated I\/R (SI\/R)-induced cellular demise. Our results demonstrated that KYNA attenuated the SI\/R-induced calcium overload as well as impairments in the mitochondrial ultrastructure. Furthermore, administration of KYNA was shown to reduce mitochondrial superoxide production and preserve mitochondrial function in cells exposed to SI\/R. Activation of the GPR35 receptors using an agonist other than KYNA rescued cardiac cells undergoing SI\/R, attenuated the apoptotic activity, and improved various parameters of mitochondrial respiration. The administration of a synthetic GPR35 antagonist in parallel with KYNA attenuated the KYNA-induced cytoprotection. Our findings provide evidence that the protective effect of KYNA against SI\/R-induced cardiac cell injury involves mitoprotective mechanisms, acting, at least in part, through the activation of GPR35 receptors.<\/jats:p>","DOI":"10.3390\/biom15101481","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:17:35Z","timestamp":1761056255000},"page":"1481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Kynurenic Acid Protects Against Myocardial Ischemia\/Reperfusion Injury by Activating GPR35 Receptors and Preserving Mitochondrial Structure and Function"],"prefix":"10.3390","volume":"15","author":[{"given":"D\u00f3ra","family":"N\u00f3gr\u00e1di-Halmi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Division of Haematology, Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Clinical Center, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Erd\u00e9lyi-Furka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Doctoral School of Experimental and Preventive Medicine, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"Cs\u00f3r\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Plechl","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-4397","authenticated-orcid":false,"given":"N\u00f3ra","family":"Igaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-9572","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-1275","authenticated-orcid":false,"given":"Marietta Zita","family":"Poles","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-0367","authenticated-orcid":false,"given":"Bern\u00e1t","family":"N\u00f3gr\u00e1di","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Biological Research Centre, Hungarian Research Network, H-6720 Szeged, Hungary"},{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Health Centre, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-2815","authenticated-orcid":false,"given":"Roland","family":"Patai","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Biological Research Centre, Hungarian Research Network, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6287-1093","authenticated-orcid":false,"given":"Tam\u00e1s Ferenc","family":"Polg\u00e1r","sequence":"additional","affiliation":[{"name":"Doctoral School of Experimental and Preventive Medicine, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Institute of Biophysics, Biological Research Centre, Hungarian Research Network, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nika","family":"Kiricsi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Health Centre, University of Szeged, H-6720 Szeged, Hungary"},{"name":"HUN-REN-SZTE Neuroscience Research Group, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-4532","authenticated-orcid":false,"given":"Ren\u00e1ta","family":"G\u00e1sp\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5792-2768","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Csont","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s00068-007-7152-z","article-title":"Ischemia-Reperfusion Injury: Pathophysiology and Clinical Implications","volume":"33","author":"Dorweiler","year":"2007","journal-title":"Eur. 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