A(2A) adenosine receptors regulate multiple organ failure after hemorrhagic shock in mice

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dc.authorid0000-0003-3616-1204
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorNémeth, Zoltán H.
dc.contributor.authorPacher, Pal
dc.contributor.authorAntonioli, Luca
dc.contributor.authorHaskó, György
dc.date.accessioned2022-11-04T10:39:23Z
dc.date.available2022-11-04T10:39:23Z
dc.date.issued2022
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractTrauma hemorrhagic shock (T/HS) is a clinical condition that causes multiple organ failure that needs rapid intervention. Restricted oxygen at the cellular level causes inflammation and subsequent cell death. Adenosine triphosphate is the universal intracellular energy currency and an important extracellular inflammatory signaling molecule. Adenosine, an endogenous nucleotide formed as a result of the breakdown of adenosine triphosphate, is also released during T/HS. Adenosine binds to four G protein-coupled receptors (A1R, A2a, A2b, A3R) called adenosine receptors or P1 receptors. In the present study, we evaluated the effect of activation, inactivation, and genetic absence of A2aR (A2aR-/- mice) on T/HS-induced multiple organ failure. Wild-type mice were pretreated (30 min before shock induction) with an agonist or antagonist and then subjected to T/HS by withdrawing arterial blood and maintaining the blood pressure between 28 and 32 mm Hg. A2aR-/- mice were subjected to T/HS in the absence of pharmacologic treatment. Neutrophil sequestration was assessed by detecting myeloperoxidase, and Evans blue dye (EBD) method was used to analyze lung permeability. Blood and lung inflammatory cytokine levels were determined by sandwich enzyme-linked immunosorbent assay. The liver enzymes aspartate aminotransferase and alanine aminotransferase were determined spectrophotometrically from plasma. Activation of the apoptotic cascade was evaluated using a mouse apoptosis array. Our results demonstrate that the selective A2aR agonist CGS21680 decreases lung neutrophil sequestration, lung proinflammatory cytokines IL-6 and TNF-?, and bronchoalveolar lavage EBD. Pretreatment with the selective antagonist ZM241385 and genetic blockade in A2aR-/- mice increased neutrophil sequestration, proinflammatory cytokine levels, and bronchoalveolar lavage fluid EBD. The myeloperoxidase level in the lung was also increased in A2aR-/- mice. We observed that antiapoptotic markers decreased significantly with the absence of A2aR in the lung and spleen after T/HS. In conclusion, our data demonstrate that activation of A2aR regulates organ injury and apoptosis in the setting of T/HS.
dc.description.sponsorshipUnited States Department of Health & Human Services, National Institutes of Health (NIH) - USAen_US
dc.identifier.citationKeleştemur, T., Németh, Z. H., Pacher, P., Antonioli, L. ve Haskó, G. (2022). A(2A) adenosine receptors regulate multiple organ failure after hemorrhagic shock in mice. Shock, 58(4), 321-331. http://doi.org/10.1097/SHK.0000000000001985
dc.identifier.doi10.1097/SHK.0000000000001985
dc.identifier.endpage331
dc.identifier.issn1073-2322
dc.identifier.issn1540-0514
dc.identifier.issue4
dc.identifier.pmid36018304
dc.identifier.scopus2-s2.0-85140272508
dc.identifier.scopusqualityQ1
dc.identifier.startpage321
dc.identifier.urihttp://doi.org/10.1097/SHK.0000000000001985
dc.identifier.urihttps://hdl.handle.net/20.500.12511/9927
dc.identifier.volume58
dc.identifier.wos000871375200010en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKeleştemur, Taha
dc.language.isoen
dc.publisherLippincott Williams and Wilkins
dc.relation.ispartofShocken_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectA2aR
dc.subjectCGS21680
dc.subjectHemorrhagic Shock
dc.subjectLung Injury
dc.subjectPurinergic Signaling
dc.subjectZM241385
dc.titleA(2A) adenosine receptors regulate multiple organ failure after hemorrhagic shock in mice
dc.typeArticle

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