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Inhibition of MicroRNA-23 Contributes to the Isoflurane-Mediated Cardioprotection Against Oxidative Stress

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Abstract

Isoflurane is one of the most frequently used volatile anesthetics in clinical practice for inhalational anesthesia. It is widely studied that isoflurane mediates cardioprotection during multiple pathological processes. However, the precise mechanisms have not been fully elucidated. Neonatal cardiomyocytes were isolated and cultured, followed by treatments with isoflurane at 0, 50, 100 or 200 µM. Rat cardiomyoblast cell line, H9c2, was treated with H2O2. Expression of miR-23 was measured by qRT-PCR. The cell survival rate of H9c2 in response to H2O2 treatments was evaluated by MTT assay. The ROS and GSH/GSSG levels were measured using Superoxide Detection Kit and GSH/GSSG Ratio Detection Assay Kit. In this study, we report an isoflurane-miR-23-antioxidant axis in cardiomyocyte. We observed that miR-23 was suppressed by isoflurane treatments at 50, 100 or 200 µM. Moreover, cardiomyocyte with isoflurane exposure was insensitive to H2O2 treatment in vitro. Inhibition of miR-23 protected cardiomyocyte against oxidative stress induced by H2O2 treatments at 30, 60, 90 or 120 µM. In addition, overexpression of miR-23 induced ROS generation over twofolds and rendered cardiomyocyte sensitive to H2O2 treatments. We demonstrate that miR-23 inhibited intracellular GSH, an antioxidant against oxidative stress. Our results reveal that with isoflurane exposure, overexpression of miR-23 rendered cardiomyocyte sensitive to H2O2 treatments at 20, 30, 40, 50 µM. Pretreatments with GSH in miR-23 overexpressing cells rescued the cell death under oxidative stress. In summary, our results illustrate that the isoflurane-mediated protection of cardiomyocytes under oxidative stress is through inhibition of miR-23. This study provides an aspect for the miRNAs-modulated cardiomyocyte sensitivity to oxidative stress, contributing to the development of therapeutic agents.

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Abbreviations

Isoflurane:

2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane

I/R:

Ischemia–reperfusion

ROS:

Reactive oxygen species

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Authors and Affiliations

  1. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Hai-jian Liu & Bin Liu

  2. Department of Anesthesiology, Zhoupu Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China

    Hai-jian Liu

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  1. Hai-jian Liu
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  2. Bin Liu
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Correspondence to Bin Liu.

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Liu, Hj., Liu, B. Inhibition of MicroRNA-23 Contributes to the Isoflurane-Mediated Cardioprotection Against Oxidative Stress. Cardiovasc Toxicol 18, 450–458 (2018). https://doi.org/10.1007/s12012-018-9455-1

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