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Dexmedetomidine alleviates H2O2-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells

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Abstract

Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H2O2 to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H2O2 significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p < 0.05, H2O2 vs. Control). Dex preconditioning alleviated these injuries induced by H2O2. Dex preconditioning significantly increased expression of protein HO-1 and decreased expressions of proteins RIPK1 and RIPK3 induced by H2O2, while all these protective effects of Dex were reversed by YOH (all p < 0.05, Dex + H2O2 vs. H2O2; and YOH + Dex + H2O2 vs. Dex + H2O2). However, YOH did not prevent this protective effect of Dex against H2O2 induced apoptosis (YOH + Dex + H2O2 vs. Dex + H2O2, p > 0.05). These findings indicated that Dex attenuates H2O2 induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.

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Acknowledgements

The authors acknowledge for Mr. Peng Xing (Shenzhen Ivy-Valued Biotechnology Co. Ltd) for technical assistance during the experiments, and acknowledge Shenzhen Ivy-Valued Biotechnology Co. Ltd. for English language editing service.

Funding

This study was supported by the funding from the National Natural Science Foundation of China (81801947) and the funding of JCYJ20180305180809671 of Shenzhen Science and Technology Innovation Committee.

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  1. Wenchao Yin and Chunyan Wang contributed equally to this study.

Authors and Affiliations

  1. Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China

    Wenchao Yin & Jinqiao Qian

  2. Department of Anesthesiology, Sichuan Provincial Orthopedic Hospital, Chengdu, 610041, Sichuan, China

    Wenchao Yin

  3. Department of Anesthesiology, Shenzhen People’s Hospital and Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College of Jinan University, Shenzhen, China

    Chunyan Wang, Wenlin Yuan & Zhongjun Zhang

  4. Department of Anesthesiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518034, China

    Yue Peng & Congcai Ren

  5. Department of Anaesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA, USA

    Hong Liu & Zhengyuan Xia

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  1. Wenchao Yin
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Yin, W., Wang, C., Peng, Y. et al. Dexmedetomidine alleviates H2O2-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells. Mol Biol Rep 47, 3629–3639 (2020). https://doi.org/10.1007/s11033-020-05456-w

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