Propofol Prevents Hippocampal Neuronal Loss and Memory Impairment in Cerebral Ischemia Injury Through Promoting PTEN Degradation

Abstract

Neuroprotective effect of propofol against cerebral ischemia injury was widely investigated. However, its mechanisms remain unclear. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is supposed as a cell survival pathway, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a negative regulator of AKT phosphorylation. Whether PTEN was involved in the protective effect of propofol against cerebral ischemia injury was not elucidated. In this study, the function of PTEN in the acute phase of cerebral ischemia injury was investigated. Our data showed that propofol promoted the PTEN degradation in the acute phase of cerebral ischemia injury and concurrently activated AKT phosphorylation. The increase of ubiquitinated PTEN caused by cerebral ischemia injury were degraded in propofol-pretreated rats. Moreover, we evidenced that proteasome activity was stimulated in propofol-treated rats. These data pointed that PTEN degradation was facilitated in the acute phase after propofol treatment possibly through activating ubiquitin-proteasome system. Therefore, we applied PTEN inhibitor-bpV before cerebral ischemia injury. Like propofol, bpV pretreatment also mitigated cerebral ischemia injury-induced cell loss in CA1 region and memory impairment. Taken together, our data suggest that PTEN degradation is neuroprotective against cerebral ischemia injury and propofol facilitates PTEN degradation to prevent hippocampal neuronal loss and memory deficit in cerebral ischemia injury.

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

“…Cerebral ischemia is divided into acute and chronic diseases (Zhao et al, ); acute cerebral ischemia is a familiar disease in the elderly, which has been paid more attention in clinic, but chronic cerebral ischemia has rarely attracted people's attention. The etiology of cerebral ischemia is closely linked to cerebral arteriosclerosis (Moroni et al, ), and chronic cerebral insufficiency is the most likely cause of dizziness, sleep disorders, and memory loss (Chen, Du, Xu, Liu, & Wang, ; Scheidt et al, ). Drug and operation are currently the cardinal treatments for cerebral ischemia (Powers et al, ; Zhang et al, ).…”

MicroRNA‑433 inhibits cell growth and induces apoptosis in human cervical cancer through PI3K/AKT signaling by targeting FAK

“…In addition, they can regulate transcription through RNA polymerase (18). Therefore, microRNAs can accelerate cell differentiation and proliferation, and promote cancerous development (5). They can also regulate the immune system, cell apoptosis, anti-apoptosis and inflammatory responses (13).…”

“…RNomics is the study of all RNA structures and functions at the genomic level, including non-coding RNA and mRNA (4). The Human Genome Project, completed in 2001, (4) marked the beginning of the post-genome era (5). It has led to our current interpretation of the composition and expression regulation of genetic information from non-coding RNA (5).…”

“…The Human Genome Project, completed in 2001, (4) marked the beginning of the post-genome era (5). It has led to our current interpretation of the composition and expression regulation of genetic information from non-coding RNA (5). Non-coding RNA, particularly microRNAs (miRNAs), is important in regulating gene expression (6).…”

HuD is a neural enhancer of global translation acting on mTORC1-responsive genes and sponged by the Y3 small non-coding RNA

“…For these reasons, attempts aimed at stimulating the mTORC1 pathway, for example with PTEN inhibitors (Chen et al, 2016;Walker and Xu, 2014) could have therapeutic potential for degenerating motor neurons. The new HuD activity we described here of mTORC1-independent global translational enhancer offers another window of opportunity, which becomes even more interesting under the light of the high modulation of HuD function offered by the sponge effect of the ncRNA Y3.…”