Dexmedetomidine protects h9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenationinduced intracellular calcium overload and apoptosis through regulating fkbp12.6/ryr2 signaling

Mei Yuan, Xiao Wen Meng, Jiao Ma, Hong Liu, Shao Yong Song, Qing Cai Chen, Hua Yue Liu, Juan Zhang, Nan Song, Fu Hai Ji, Ke Peng

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Purpose: Intracellular calcium ([Ca2+]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca2+ signaling. Methods: H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca2+]i, cell apoptosis, and the expression of 12.6-kd FK506binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed. Results: Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca2+]i level and apoptosis rate, down-regulated expression of FKBP12.6, and upregulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX. Conclusion: This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca2+]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.

Original languageEnglish (US)
Pages (from-to)3137-3149
Number of pages13
JournalDrug Design, Development and Therapy
Volume13
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Apoptosis
  • Dexmedetomidine
  • FKBP12.6/RyR2
  • H9c2 cardiomyocytes
  • Intracellular calcium overload
  • Oxygen-glucose deprivation/ reoxygenation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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