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• W3214749582 abstract "Introduction: Ischemic injury to the heart induces mitochondrial dysfunction due to an increase in oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle and is essential for repairing damaged plasma membranes by interacting with the membrane lipid phosphatidylserine. We have previously shown that mg53-/- mice are more susceptible to ischemia-reperfusion injury, and treatment with exogenous recombinant human MG53 (rhMG53) reduces infarct damage, restores cardiac function and preserves mitochondrial membrane potential. Hypothesis: We hypothesize MG53 preserves mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondrial membrane repair, preventing the formation of superoxides and mitophagy. Methods: Fluorescent imaging and western blotting experiments were conducted after ischemic injury in vivo and in vitro to measure the formation of superoxides and activation of mitophagy. A lipid binding assay was used to determine MG53’s ability to bind to CL. Transfection of murine cardiomyocyte cells with the mitochondria-targeted mt-mKeima was used to measure engulfment of the mitochondria by the lysosome. Results: We found that recombinant human MG53 (rhMG53) delivered prior ischemia/reperfusion translocated to the mitochondria both in vivo and in vitro. Additionally, superoxide generation was reduced by rhMG53 treatment using ex vivo and in vitro models. A lipid binding assay revealed rhMG53 binds to CL. Treating with rhMG53 inhibited mitophagy after ischemia/reperfusion, as demonstrated by the reduction of mitochondria in the lysosome after rhMG53 treatment and a reduction in mitochondria-bound parkin, a key mediator of mitophagy. Conclusions: In this study we provide evidence that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53’s interactions with mitochondria could be an attractive avenue for the development of MG53 as a targeted protein therapy for cardioprotection." @default.
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• W3214749582 date "2021-11-16" @default.
• W3214749582 modified "2023-09-26" @default.
• W3214749582 title "Abstract 13835: MG53 Preserves Mitochondrial Integrity of Cardiomyocytes in Pre-Clinical Models of Ischemia Reperfusion-Induced Oxidative Stress" @default.
• W3214749582 doi "https://doi.org/10.1161/circ.144.suppl_1.13835" @default.
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