Dexmedetomidine protects hepatic cells against oxygen-glucose deprivation/reperfusion injury via lncRNA CCAT1

Cell Biol Int. 2018 Sep;42(9):1250-1258. doi: 10.1002/cbin.10996. Epub 2018 Jul 2.

Abstract

Dexmedetomidine (Dex) protects different cell types during hypoxia or ischemia-reperfusion injury by inhibiting cell apoptosis. However, the underlying mechanism and its impact on hepatic ischemia reperfusion injury are still not known. In this study, we established a model of oxygen-glucose deprivation/reperfusion (OGD/R) injury in hepatocyte HL7702 cells, and studied the impact of Dex on cell proliferation, apoptosis, and cell cycle during OGD/R. In addition, we explored the role of CCAT1 in this process. We found that Dex increased cell proliferation and inhibited cell apoptosis during OGD/R, in a concentration-dependent manner. Dex partially reversed the OGD-inhibited expression of lncRNA CCAT1. Knockdown of CCAT1 by siRNA inhibited Dex-mediated protection against OGD/R-induced injury and promoted cell apoptosis, caspase-3 expression and cell cycle arrest in the G0/G1 phase, and inhibited cell proliferation and cyclin D1 expression. In contrast, overexpression of CCAT1 by pcDNA3.0-CCAT1 enhanced Dex-mediated protection against OGD/R-induced cell injury. Thus, Dex protects hepatocytes against OGD/R injury by upregulating lncRNA CCAT1. This study suggests a novel role of CCAT1 in ischemia reperfusion injury, and lays the framework for future studies.

Keywords: HL7702 cells; cell apoptosis; dexmedetomidine; lncRNA CCAT1; oxygen-glucose deprivation/reperfusion injury.

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dexmedetomidine / metabolism
  • Dexmedetomidine / pharmacology*
  • Glucose / metabolism
  • Hepatocytes / metabolism*
  • Humans
  • Hypoxia
  • Liver / metabolism
  • Oxygen / metabolism
  • Protective Agents / pharmacology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism

Substances

  • CCAT1 long noncoding RNA, human
  • Protective Agents
  • RNA, Long Noncoding
  • Dexmedetomidine
  • Glucose
  • Oxygen