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Although the endogenous tryptophan metabolite kynurenic acid (KYNA) has been shown to exert protection against I\/R injury, its mechanism of action at the cellular and molecular level is not well understood yet. Therefore, we examined the potential involvement of antiapoptotic mechanisms, as well as N-methyl-D-aspartate (NMDA) receptor modulation in the protective effect of KYNA in cardiac cells exposed to simulated I\/R (SI\/R). KYNA was shown to attenuate cell death induced by SI\/R dose-dependently in H9c2 cells or primary rat cardiomyocytes. Analysis of morphological and molecular markers of apoptosis (i.e., membrane blebbing, apoptotic nuclear morphology, DNA double-strand breaks, activation of caspases) revealed considerably increased apoptotic activity in cardiac cells undergoing SI\/R. The investigated apoptotic markers were substantially improved by treatment with the cytoprotective dose of KYNA. Although cardiac cells were shown to express NMDA receptors, another NMDA antagonist structurally different from KYNA was unable to protect against SI\/R-induced cell death. Our findings provide evidence that the protective effect of KYNA against SI\/R-induced cardiac cell injury involves antiapoptotic mechanisms, that seem to evoke independently of NMDA receptor signaling.<\/jats:p>","DOI":"10.1007\/s10495-024-02004-w","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T08:01:51Z","timestamp":1723881711000},"page":"1483-1498","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Kynurenic acid protects against ischemia\/reperfusion injury by modulating apoptosis in cardiomyocytes"],"prefix":"10.1007","volume":"29","author":[{"given":"Ren\u00e1ta","family":"G\u00e1sp\u00e1r","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"N\u00f3gr\u00e1di-Halmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vir\u00e1g","family":"Demj\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Di\u00f3szegi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00f3ra","family":"Igaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vincze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Pipicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nika","family":"Kiricsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Csont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"2004_CR1","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1007\/s00068-007-7152-z","volume":"33","author":"B Dorweiler","year":"2007","unstructured":"Dorweiler B, Pruefer D, Andrasi TB et al (2007) Ischemia-reperfusion injury. 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