The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats

PLoS One. 2014 Nov 18;9(11):e113305. doi: 10.1371/journal.pone.0113305. eCollection 2014.

Abstract

Hydrogen sulfide (H2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H2S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpression of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H2S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H2S on hepatic I/R injury in the old rats. This study reveals the different effects of H2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H2S in miR-34a modulation of the Nrf-2 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Blotting, Western
  • Cells, Cultured
  • Gene Expression / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hydrogen Sulfide / blood
  • Hydrogen Sulfide / pharmacology*
  • Liver / blood supply
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • MicroRNAs / genetics*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Protective Agents / pharmacology
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / genetics
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sulfides / blood
  • Sulfides / pharmacology

Substances

  • MIRN34 microRNA, rat
  • MicroRNAs
  • NF-E2-Related Factor 2
  • Protective Agents
  • Sulfides
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • sodium bisulfide
  • Hydrogen Sulfide

Grant support

This work was supported by grant from the Priority Academic Program of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.