Department of Physiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences, School of Medicine, Wuhan University, 185 Donghu Street, Wuhan, 430071, China.
Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, 430060, China.
Neurochem Res. 2018 Jul;43(7):1424-1438. doi: 10.1007/s11064-018-2558-z. Epub 2018 Jun 7.
Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is a commercially available PTEN inhibitor. Previous studies from us and others have shown that bpV(pic) confers neuroprotection in cerebral ischemia injury. We set up to determine whether ERK 1/2 activation plays a role in bpV(pic)-induced neuroprotective effect in cerebral ischemia injury. We found that the phosphorylation levels of Akt (p-AKT) and ERK1/2 (p-ERK 1/2) were down-regulated after cerebral ischemia-reperfusion injury. The injection of bpV(pic) after injury not only increased the level of p-AKT but also the level of p-ERK 1/2. While the inhibition of PTEN mediated the up-regulatation of p-AKT and p-ERK 1/2 by bpV(pic). Interestingly, the ERK 1/2 activation induced by bpV(pic) was also independent of the inhibition of PTEN. Our results indicate that bpV(pic) protects against OGD-induced neuronal death and promotes the functional recovery of stroke animals through PTEN inhibition and ERK 1/2 activation, respectively. This study suggests that the effect of bpV(pic) on ERK 1/2 signaling should be considered while using bpV(pic) as a PTEN inhibitor.
双（吡啶-2-羧酸）过钒（bpV(pic)）是一种市售的 PTEN 抑制剂。我们和其他人的先前研究表明，bpV(pic)在脑缺血损伤中具有神经保护作用。我们旨在确定 ERK1/2 的激活是否在 bpV(pic)诱导的脑缺血损伤中的神经保护作用中发挥作用。我们发现，脑缺血再灌注损伤后 Akt（p-AKT）和 ERK1/2（p-ERK 1/2）的磷酸化水平下调。损伤后注射 bpV(pic)不仅增加了 p-AKT 的水平，而且增加了 p-ERK 1/2 的水平。而 PTEN 的抑制介导了 bpV(pic)对 p-AKT 和 p-ERK 1/2 的上调。有趣的是，bpV(pic)诱导的 ERK1/2 激活也独立于 PTEN 的抑制。我们的结果表明，bpV(pic)通过抑制 PTEN 和激活 ERK1/2 分别保护 OGD 诱导的神经元死亡和促进中风动物的功能恢复。本研究提示，在使用 bpV(pic)作为 PTEN 抑制剂时，应考虑 bpV(pic)对 ERK1/2 信号的影响。
