biostudies-literatureUnknown12Zhao DIntracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we examined the effect of bpV[pic] in the rat ICH model <i>in vivo</i> and the hemin-induced injury model in rat cortical cultures. The rat model of ICH was created by injecting autologous blood into the striatum, and bpV[pic] was intraperitoneally injected. The effects of bpV[pic] were evaluated by neurological tests, Fluoro-Jade C (FJC) staining, and Nissl staining. We demonstrate that bpV[pic] attenuates ICH-induced brain injury <i>in vivo</i> and hemin-induced neuron injury <i>in vitro</i>. The expression of E2F1 was increased, but ?-catenin expression was decreased after ICH, and the altered expressions of E2F1 and ?-catenin after ICH were blocked by bpV[pic] treatment. Our results further show that bpV[pic] increases ?-catenin expression through downregulating E2F1 in cortical neurons and prevents hemin-induced neuronal damage through E2F1 downregulation and subsequent upregulation of ?-catenin. By testing the effect of PTEN-siRNA, PTEN cDNA, or combined use of ERK1/2 inhibitor and bpV[pic] in cultured cortical neurons after hemin-induced injury, we provide evidence suggesting that PTEN inhibition by bpV[pic] confers neuroprotection through E2F1 and ?-catenin pathway, but the neuroprotective role of ERK1/2 activation by bpV[pic] cannot be excluded.Frontiers in molecular neuroscience281https://www.ebi.ac.uk/biostudies/studies/S-EPMC6906195biostudies-literaturePTEN Inhibition Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury Through PTEN/E2F1/?-Catenin Pathway.PMC6906195Qin XPWan QZhang ZFLiao XYLei YLiu RZhao DChen SFCheng JfalsePTEN Inhibition Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury Through PTEN/E2F1/?-Catenin Pathway.Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we examined the effect of bpV[pic] in the rat ICH model <i>in vivo</i> and the hemin-induced injury model in rat cortical cultures. The rat model of ICH was created by injecting autologous blood into the striatum, and bpV[pic] was intraperitoneally injected. The effects of bpV[pic] were evaluated by neurological tests, Fluoro-Jade C (FJC) staining, and Nissl staining. We demonstrate that bpV[pic] attenuates ICH-induced brain injury <i>in vivo</i> and hemin-induced neuron injury <i>in vitro</i>. The expression of E2F1 was increased, but ?-catenin expression was decreased after ICH, and the altered expressions of E2F1 and ?-catenin after ICH were blocked by bpV[pic] treatment. Our results further show that bpV[pic] increases ?-catenin expression through downregulating E2F1 in cortical neurons and prevents hemin-induced neuronal damage through E2F1 downregulation and subsequent upregulation of ?-catenin. By testing the effect of PTEN-siRNA, PTEN cDNA, or combined use of ERK1/2 inhibitor and bpV[pic] in cultured cortical neurons after hemin-induced injury, we provide evidence suggesting that PTEN inhibition by bpV[pic] confers neuroprotection through E2F1 and ?-catenin pathway, but the neuroprotective role of ERK1/2 activation by bpV[pic] cannot be excluded.2019-01-01T00:00:00Z20192021-02-20T19:26:15Z2020-05-21T23:51:35ZS-EPMC69061953186682010.3389/fnmol.2019.00281