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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00281

PTEN Inhibition Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury Through PTEN/E2F1/β-catenin Pathway

 Qi Wan1*,  Dan Zhao2,  Xingping Qin3, Feng S. Chen4, Yu X. Liao4, Jing Cheng4, Rui Liu4,  Yang Lei4 and Feng Z. Zhang2*
  • 1Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, China
  • 2Hubei University of Medicine, China
  • 3Department of Neurosurgery, Renmin Hospital of Wuhan University, China
  • 4Department of Physiology, Faculty of Medical Sciences, Wuhan University, China

Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that bpV[pic] inhibits PTEN and activates ERK 1/2 respectively. In this study, we examined the effect of bpV[pic] in the rat ICH model in vivo 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 in vivo and hemin-induced neuron injury in vitro. The expression of E2F1 was increased but β-catenin expression was decreased after ICH, and the altered expression of E2F1 and β-catenin after ICH was blocked by bpV[pic] treatment. Our results further show that bpV[pic] increases β-catenin expression through down-regulating E2F1 in cortical neurons, and prevents hemin-induced neuronal damage through E2F1 down-regulation and subsequent up-regulation of β-catenin. By testing the effect of PTEN-siRNA, PTEN cDNA or combined use of ERK 1/2 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 β-catenin pathway, but the neuroprotective role of ERK 1/2 activation by bpV[pic] cannot be excluded.

Keywords: intracerebral hemorrhage, PTEN (phosphatase and tensin homologue deleted on chromosome 10), E2F1, β-Catenin (B-Catenin), Brain Injury

Received: 18 Jul 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Wan, Zhao, Qin, Chen, Liao, Cheng, Liu, Lei and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Qi Wan, Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, China, qwan@whu.edu.cn
PhD. Feng Z. Zhang, Hubei University of Medicine, Shiyan, Hubei, China, iq2277@163.com