Dexmedetomidine alleviates H2O2-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells
- 27 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Biology Reports
- Vol. 47 (5), 3629-3639
- https://doi.org/10.1007/s11033-020-05456-w
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.Keywords
Funding Information
- National Natural Science Foundation of China (81801947)
- Shenzhen Science and Technology Innovation Committee (JCYJ20180305180809671)
This publication has 40 references indexed in Scilit:
- Programmed necrosis in cardiomyocytes: mitochondria, death receptors and beyondBritish Journal of Pharmacology, 2018
- Programmed necrosis in heart disease: Molecular mechanisms and clinical implicationsJournal of Molecular and Cellular Cardiology, 2018
- Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitroRedox Biology, 2017
- Acute Myocardial InfarctionThe New England Journal of Medicine, 2017
- CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosisNature Medicine, 2016
- Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion InjuryBioMed Research International, 2015
- MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADDCirculation Research, 2015
- Myocardial ischemia-reperfusion injury: a neglected therapeutic targetJCI Insight, 2013
- Programmed Necrosis, Not Apoptosis, in the HeartCirculation Research, 2011
- Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion InjuryPhysiological Reviews, 2008