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

Wenchao Yin, Chunyan Wang, Yue Peng, Wenlin Yuan, Zhongjun Zhang, Hong Liu, Zhengyuan Xia, Congcai Ren, Jinqiao Qian

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3629-3639
Number of pages11
JournalMolecular Biology Reports
Volume47
Issue number5
DOIs
StatePublished - May 1 2020
Externally publishedYes

Keywords

  • Dexmedetomidine
  • Necroptosis
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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