Abstract. Reactive oxygen species (ROS) are involved in myocardial injury. ROS are known to inactivate lipid phosphatase and tension homolog on chromosome 10 (PTEN), an enzyme that increases apoptosis in neonatal cardiomyocytes. BpV(pic) and bpV(phen), two bisperoxovanadium molecules and PTEN inhibitors, may be involved in limiting myocardial infarction. To compare the protective effects of bpV(pic) and bpV(phen) on ROS-induced cardiomyocyte injury and their possible mechanisms, we selected two popular models of hypoxia/reoxygenation (H/R) and H 2 O 2 -induced injury in H9c2 cardiomyoblasts to investigate their effects against injury. We found that pre-treatment with bpV(pic) and bpV(phen) increased the viability and protected the morphology of H9c2 cells under the conditions of H/R and H 2 O 2 by inhibiting LDH release, apoptosis and caspases 3/8/9 activities. However, their respective inhibitory abilities in the two models were different, suggesting that the quantity of ROS from the two models might be different. However, the conflict between ROS and PTEN may affect the action of bpV(pic) and bpV(phen). Taken together, the results demonstrate that bpV(pic) and bpV(phen) have inhibitory effects on oxidative stress-induced cardiomyocyte injury that may be partially modulated by the action of ROS on PTEN.
IntroductionMyocardial ischemia/reperfusion injury (MIRI), which may lead to various complications, including myocardial infarction, cardiac contractile dysfunction and arrhythmia (1-4), has become an increasingly common problem in clinics. However, few strategies directed against MIRI have been tested under clinical conditions (5,6). Recently, a new finding showed that the pharmacological inhibition of lipid phosphatase and tension homolog on chromosome 10 (PTEN) limited myocardial infarct size and improved left ventricular function post-infarction (7). Moreover, protein tyrosine phosphatase inhibitors and bisperoxovanadium molecules (bpV) inhibited PTEN specifically at low concentrations (8). The protective effects of bpV(HOpic) on myocardial injury in vitro and in vivo have been observed in previous studies (7). However, other bpV molecules have not been studied and compared for their actions against MIRI.Based on the cellular mechanisms of ischemia/reperfusion injury that have been extensively explored (9-11), reactive oxygen species (ROS) generated with the re-admission of oxygen are considered the first and main cause of ischemia/ reperfusion injury (12). Thus, scavenging excessive ROS and restoring the reduction-oxidation (redox) balance in the body is an important strategy in inhibiting reperfusion injury, as the redox balance is the solid physiological condition in humans from birth (13,14), and, despite evolution, this balance has always been conserved in all organisms (15,16).Hydrogen dioxide (H 2 O 2 ), a famous ROS, inhibits the lipid phosphatase activity of the tumour suppressor PTEN enzyme (17), which suggests that when produced under pathological conditions, such as during MIRI or chronic inflamm...