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  • miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner.

miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner.

Biomedicines (2022-01-22)
Gurdeep Marwarha, Øystein Røsand, Nathan Scrimgeour, Katrine Hordnes Slagsvold, Morten Andre Høydal
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
AC16 Human Cardiomyocyte Cell Line, AC16 Human Cardiomyocytes can be serially passaged and can differentiate when cultured in mitogen-free medium. The cells may be used to study developmental regulation of cardiomyocytes.
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Anti-Rabbit IgG (whole molecule)–Alkaline Phosphatase antibody produced in goat, affinity isolated antibody, buffered aqueous glycerol solution
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Anti-RIPK1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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Caspase-3 Inhibitor I, The Caspase-3 Inhibitor I, also referenced under CAS 169332-60-9, controls the biological activity of Caspase-3. This small molecule/inhibitor is primarily used for Cancer applications.
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Caspase-8 Inhibitor II, The Caspase-8 Inhibitor II controls the biological activity of Caspase-8. This small molecule/inhibitor is primarily used for Cancer applications.
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Cytochrome c Release Apoptosis Assay Kit