CORM-3 mitigates hypoxia/reoxygenation-induced injury in neonatal rat cardiomyocytes by regulating mitochondrial-mediated apoptosis and complex IV activity

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dc.contributor.authorQingsheng Niu
dc.contributor.authorXiaojuan Yang
dc.contributor.authorJunwei Zheng
dc.contributor.authorXiaohong Wang
dc.contributor.authorFang Du
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2026-01-07T16:33:05Z
dc.date.available2026-01-07T16:33:05Z
dc.date.issued2026
dc.description.abstractBackground. Myocardial ischemia-reperfusion injury (MIRI) is a major contributor to myocardial infarction and leads to significant myocardial dysfunction. Mitochondria, crucial for cellular energy production, are particularly susceptible to damage during ischemia/reperfusion (I/R) events. Carbon monoxide-releasing molecule-3 (CORM-3), a water-soluble compound that releases carbon monoxide (CO), has demonstrated multiple protective effects against I/R injury. Mitochondria are recognized as selective targets for CO’s protective actions in cells. Purpose. This study aimed to explore whether CORM-3 mitigates cardiomyocyte injury during hypoxia/reoxygenation (H/R) by regulating the mitochondrial-mediated apoptosis pathway and mitochondrial respiration. Methods. Neonatal rat cardiomyocytes were cultured and randomly assigned into four groups: control group, H/R group (hypoxia for three hours followed by reoxygenation for six hours), CORM-3 group, and inactivated CORM-3 (iCORM-3) group. CORM-3 and iCORM-3 (12.5 μmol/L) were administered at the onset of hypoxia. Mitochondrial ultrastructure was assessed using transmission electron microscopy. The protein levels of caspase-3, caspase-9, mitochondrial cytochrome c, and cytosolic cytochrome c were analyzed via western blot. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were measured by flow cytometry. ATP levels were quantified using an ATP Assay Kit, and mitochondrial respiratory chain complex IV activity was determined using a cytochrome oxidase activity colorimetric assay kit. Results. CORM-3 effectively reduced myocardial mitochondrial structural damage induced by H/R and downregulated the expression of caspase-3, caspase-9, and cytosolic cytochrome c. Moreover, CORM-3 inhibited cytochrome c release from mitochondria and enhanced mitochondrial membrane potential. Additionally, CORM-3 diminished ROS production and increased the activity of mitochondrial respiratory complex IV in cardiomyocytes. CORM-3 also alleviated the decline in ATP levels following H/R. The protective effects were lost when using inactivated CORM-3 (iCORM-3), suggesting that CO is the active mediator. Conclusion. The results indicate that CORM-3 effectively alleviates myocardial injury during H/R by inhibiting mitochondria-mediated apoptosis and enhancing mitochondrial respiratory function
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dc.format.extent12
dc.identifier.doihttps://doi.org/10.14670/HH-18-941
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/184309
dc.languageeng
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHypoxia/reoxygenation
dc.subjectCardiomyocyte mitochondria
dc.subjectApoptosis
dc.subjectRespiration
dc.subjectCarbon monoxide-releasing molecule
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleCORM-3 mitigates hypoxia/reoxygenation-induced injury in neonatal rat cardiomyocytes by regulating mitochondrial-mediated apoptosis and complex IV activity
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.41, Nº2, (2026)