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

Abstract

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.

Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved

“…The mechanism were also previously explored, including by inhibiting high mobility group box 1 expression (Wang et al, 2012), increasing HSP70, caveolae formation and caveolin-3 (Tsutsumi et al, 2014), activating PI3 kinase and/or Rho kinase pathways (Zhu et al, 2005), opening the mitoK(ATP) channel (Shinohara et al, 2007), activation of PKC (Yamanaka et al, 2003), induction of thioredoxin and the activation of transcription factors such as NFkappaB and AP-1 (Hirota et al, 2000).In this study, GGA showed its ability to inhibit the neurological impairment, brain edema, inflammation, oxidative injury and neuron damage induced by cerebral I/R. To explore the molecular mechanism of GGA action, unlike the previous studies, we focused on hsp90, another HSP induced by GGA, and eNOS, an important cerebrovascular Hsp90, an adenosine triphosphate-dependent chaperone, is the major soluble protein of the cell.…”

Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes

“…Ischemic reperfusion (IR) triggers the disturbance of microcirculation, a primary cause of cardiac failure and mortality following cardiac surgeries (1,2). Microcirculatory disturbances include endothelial cell injury, production of oxygen free radicals, energy supply reduction and myocardiocyte apoptosis (3).…”

Protective effect of proanthocyanidins on anoxia-reoxygenation injury of myocardial cells mediated by the PI3K/Akt/GSK-3β pathway and mitochondrial ATP-sensitive potassium channel

“…Myocardial ischemia reperfusion injury is a highly complex process, and currently there are several key pathogenic mechanisms that are considered to be involved, including oxidative stress injury, intracellular calcium overload, cell apoptosis, cellular energy loss and activation of neutrophil inflammatory reaction (4). Ischemia reperfusion injury also involves multiple regulatory mechanisms, including the activation and inactivation of signaling pathways (5).…”