dc.contributor.author | Marwarha, Gurdeep | |
dc.contributor.author | Røsand, Øystein | |
dc.contributor.author | Scrimgeour, Nathan Robert | |
dc.contributor.author | Slagsvold, Katrine Hordnes | |
dc.contributor.author | Høydal, Morten | |
dc.date.accessioned | 2023-01-17T15:14:24Z | |
dc.date.available | 2023-01-17T15:14:24Z | |
dc.date.created | 2022-03-02T18:40:36Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/11250/3044136 | |
dc.description.abstract | Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia–reperfusion (I/R) injury. The master hypoxamiR, microRNA-210 (miR-210), is considered the primary driver of the cellular response to hypoxic stress. However, to date, no consensus has emerged with regards to the polarity of the miR-210-elicited cellular response, as miR-210 has been shown to exacerbate as well as attenuate hypoxia-driven apoptotic cell death. Herein, in AC-16 cardiomyocytes subjected to hypoxia-reoxygenation (H-R) stress, we unravel novel facets of miR-210 biology and resolve the biological response mediated by miR-210 into the hypoxia and reoxygenation temporal components. Using transient overexpression and decoy/inhibition vectors to modulate miR-210 expression, we elucidated a Janus role miR-210 in the cellular response to H-R stress, wherein miR-210 mitigated the hypoxia-induced apoptotic cell death but exacerbated apoptotic cell death during cellular reoxygenation. We further delineated the underlying cellular mechanisms that confer this diametrically opposite effect of miR-210 on apoptotic cell death. Our exhaustive biochemical assays cogently demonstrate that miR-210 attenuates the hypoxia-driven intrinsic apoptosis pathway, while significantly augmenting the reoxygenation-induced caspase-8-mediated extrinsic apoptosis pathway. Our study is the first to unveil this Janus role of miR-210 and to substantiate the cellular mechanisms that underlie this functional duality. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.volume | 10 | en_US |
dc.source.journal | Biomedicines | en_US |
dc.source.issue | 1 | en_US |
dc.identifier.doi | 10.3390/biomedicines10010042 | |
dc.identifier.cristin | 2007094 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |