@article{APS9857,
author = {Min ZHU and Ming LIU and Qi-lin GUO and Cui-qing ZHU and Jing-chun GUO},
title = {Prolonged DADLE exposure epigenetically promotes Bcl-2 expression and elicits neuroprotection in primary rat cortical neurons via the PI3K/Akt/NF-κB pathway},
journal = {Acta Pharmacologica Sinica},
volume = {39},
number = {10},
year = {2018},
keywords = {},
abstract = {Both in vivo and in vitro studies have shown the beneficial effects of the delta-opioid receptor (DOR) on neurodegeneration in hypoxia/ischemia. We previously reported that DOR stimulation with [(D-Ala2, D-Leu5) enkephalin] (DADLE), a potent DOR agonist, for both a short (minutes) and long (days) time has notable protective effects against sodium azide (NaN3)-induced cell injury in primary cultured rat cortical neurons. We further demonstrated that short-term DADLE stimulation increased neuronal survival through the PKC-mitochondrial ERK pathway. However, the mechanisms underlying long-term neuroprotection by DADLE remain unclear. Here, we showed that DOR stimulation with DADLE (0.1 μmol/L) for 2 d selectively activates the PI3K/Akt/NF-κB pathway in NaN3-treated neurons; this activation increased Bcl-2 expression, attenuated Cyto c release and promoted neuronal survival. Further investigation revealed that sustained DADLE stimulation increased Bcl-2 expression by enhancing NF-κB binding to the Bcl-2 promoter and upregulating the histone acetylation levels of the Bcl-2 promoter. Our results demonstrate that prolonged DADLE exposure epigenetically promotes Bcl-2 expression and elicits neuroprotective effects in the NaN3 model via the PI3K/Akt/NF-κB pathway.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9857}
}