Geranylgeranylacetone protects against myocardial ischemia and reperfusion injury by inhibiting high-mobility group box 1 protein in rats

Mol Med Rep. 2012 Feb;5(2):521-4. doi: 10.3892/mmr.2011.666. Epub 2011 Nov 4.

Abstract

The high mobility group box 1 (HMGB1) protein plays an important role in myocardial ischemia and reperfusion (I/R) injury. Geranylgeranylacetone (GGA), a heat shock protein 72 inducer, has been reported to reduce myocardial I/R injury. The aim of this study was to investigate the cardioprotective mechanism of GGA during myocardial I/R injury in rats. Anesthetized male rats were treated once with GGA (200 mg/kg, p.o.) 24 h before ischemia, and subjected to ischemia for 30 min, followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting. The results showed that pre-treatment with GGA (200 mg/kg) significantly reduced the infarct size and the levels of LDH and CK after 4 h of reperfusion (all P<0.05). GGA also significantly inhibited the increase in MDA levels and the decrease in SOD levels (both P<0.05). Meanwhile, GGA considerably suppressed the expression of HMGB1 induced by I/R. The present study suggests that GGA is capable of attenuating myocardial I/R injury by inhibiting HMGB1 expression.

Keywords: geranylgeranylacetone; high-mobility group box 1 protein; myocardial ischemia and reperfusion.

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Cardiotonic Agents / therapeutic use
  • Creatine Kinase / metabolism
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Gene Expression Regulation / drug effects*
  • HMGB1 Protein / antagonists & inhibitors*
  • HMGB1 Protein / metabolism
  • HSP72 Heat-Shock Proteins / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Myocardial Ischemia / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Superoxide Dismutase / metabolism

Substances

  • Cardiotonic Agents
  • Diterpenes
  • HMGB1 Protein
  • HSP72 Heat-Shock Proteins
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Superoxide Dismutase
  • Creatine Kinase
  • geranylgeranylacetone