bpV(HOpic) shows selective inhitory effect on PTP andPTEN (IC50 = 14 nM) and acts as an insulin mimic. It also can prevent myocardial ischemia-reperfusion injury by enhancing PI3K/Akt signaling.
The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that inhibit cell survival and proliferation by inactivating PI 3-kinase-dependent signaling pathway. bpV (HOpic) is a vanadate derivative that inhibits PTEN with an IC50 value of 14 nM. In primary cardiomyocytes incubated with bpV (HOpic) without the exposure to simulated ischemia-reperfusion (SIR) for 2 hours, bpV (HOpic) at 10, 15, and 20 μM decreased the percentage of trypan-positive cells compared with non-bpV-treated cells. The maximal effect of bpV (HOpic) on the suppression of cell death was achieved at 15 μM. The cell viability as measured by MTT assay was significantly improved by bpV (HOpic) at 5 – 20 μM in cells with or without SIR. The effect of bpV (HOpic) on cardiomyocytes apoptosis was determined by TUNEL assay, in which bpV (HOpic) at 10, 15, and 20 μM decreased apoptosis in cells without SIR, whereas the anti-apoptotic effect of bpV (HOpic) in cells exposed to SIR was observed at 5, 10, and 15 μM. In rats received bpV (HOpic) before I30m and R4h, the myocardial infarct size was reduced compared to control group, and the maximal effect of bpV (HOpic) was achieved at 1.0 mg/kg. However, the protective effect of bpV (HOpic) on reducing myocardial infarct size was abrogated by wortmannin and L-NAME. In rats treated with bpV (HOpic) (1.0 mg/kg) either before ischemia (BpV-BI) or before reperfusion (BpV-BR), bpV (HOpic) reduced the increase of the left ventricular internal diameter in diastole and in systole after the I/R injury. In rats received 1.0 mg/kg bpV (HOpic) one hour before ischemia, the PTEN activity was significantly reduced at 30 m of ischemia and 4 and 12h of reperfusion.
作用机制
bpV (HOpic) acts a PTEN inhibitor by interacting with the active center of PTEN, the CX5R motif.
Terminated(Results were not pr... 展开 >>omising) 收起 <<
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United States, Colorado
... 展开 >>
Fertility Laboratories of Colorado
Lone Tree, Colorado, United States, 80124
National Foundation for Fertility Research
Lone Tree, Colorado, United States, 80124 收起 <<
Terminated(Results were not pr... 展开 >>omising) 收起 <<
-
United States, Colorado
... 展开 >>
Fertility Laboratories of Colorado
Lone Tree, Colorado, United States, 80124
National Foundation for Fertility Research
Lone Tree, Colorado, United States, 80124 收起 <<
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