Effects of bpV(pic) and bpV(phen) on H9c2 cardiomyoblasts during both hypoxia/reoxygenation and H2O2-induced injuries

Abstract

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...

Loss of cell polarity regulated by PTEN/Cdc42 enrolled in the process of Hepatopulmonary Syndrome

“…To determine if increased activity of Cdc42 might be controlled by PTEN activation, Cdc42 activity was analysed in PMVECs after treatment with BpV(pic), an inhibitor of PTEN by blocking the phosphorylation of PTEN. 25 First, we confirmed that BpV(pic) treatment successfully inhibited the phosphorylation of PTEN (P < 0.05) in PMVECs (Figure 5C and D). Consistent with our hypothesis, the levels of activated Cdc42 diminished in the CBDL group (P < 0.05) (Figure 5E and F).…”

PTEN Inhibition Facilitates Diabetic Corneal Epithelial Regeneration by Reactivating Akt Signaling Pathway

“… 36 – 38 The PTEN inhibitor bpv(Pic) was reported to promote neurite outgrowth, 39 bpv(Pic) provides neuroprotection against oxidative stress and neurotoxicity in Alzheimer's disease, 40 and bpv(Pic) and bpv(Phen) have protective effects on oxidative stress-induced cardiomyocyte injury. 41 In addition, PTEN inhibition not only functions as a neuroprotective factor in the nervous system, but also has many functions in wound repair, such as regulating the migration of a variety of epithelial cells. PTEN inhibitors were associated with wound healing in many models, PTEN inhibition improves wound healing in lung epithelia or corneal epithelium injury by enhancing migration, 18 , 42 bpv(Pic) promotes proliferation and alleviates senescence to stimulate skin renewal, 43 and bpv (Phen) reverses HG-induced apoptosis in human umbilical vascular endothelial cells.…”

A method to control phosphoinositides and to analyze PTEN function in living cells using voltage sensitive phosphatases

“…In that study, more indirect methods like assessing the phosphorylation state of Akt/PKB were used, whereas we directly monitored PTEN's substrate PI(3,4,5)P 3 to determine the effect of these inhibitors in living cells. The bpV compounds have been used to study the involvement of PTEN in signaling, proliferation, apoptosis, and neurogenesis (Band et al, 1997 ; Batty et al, 2007 ; Pi et al, 2012 ; Tian et al, 2012 ; Becker et al, 2013 ); however, higher concentrations (200 nM–100 μM) were required. We found comparable concentrations to effectively inhibit PTEN activity in our live cell assay.…”