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

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.
Authors	Neng Wang, Xinwen Min, Dongfeng Li, Peigen He, Libin Zhao
Journal	Molecular medicine reports (Mol Med Rep) Vol. 5 Issue 2 Pg. 521-4 (02 2012) ISSN: 1791-3004 [Electronic] Greece
PMID	22075975 (Publication Type: Journal Article)
Chemical References	Cardiotonic Agents Diterpenes HMGB1 Protein HSP72 Heat-Shock Proteins Malondialdehyde L-Lactate Dehydrogenase Superoxide Dismutase Creatine Kinase geranylgeranylacetone
Topics	Animals Cardiotonic Agents (pharmacology, therapeutic use) Creatine Kinase (metabolism) Diterpenes (pharmacology, therapeutic use) Gene Expression Regulation (drug effects) HMGB1 Protein (antagonists & inhibitors, 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)

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