氮氧化物4
自噬
内质网
未折叠蛋白反应
NADPH氧化酶
吗啡
细胞生物学
加巴能
线粒体
化学
活性氧
药理学
医学
生物
内科学
细胞凋亡
生物化学
受体
作者
Xuyang Xiao,Jing Yang,Qian Bai,Zhitao Wang,Yan Chen,Yue Si,Yaowei Xu,Zhisong Li,Huilian Bu
出处
期刊:Research Square - Research Square
日期:2023-05-09
标识
DOI:10.21203/rs.3.rs-2890365/v1
摘要
Abstract Morphine tolerance is one of the current challenging issues in the treatment of chronic pain. Recent studies have shown that ROS derived by NADPH oxidase (NOX) and endoplasmic reticulum (ER) stress is participated in the development of morphine tolerance. However, which NOX subtype initiates the ER stress during the development of morphine tolerance is not fully clear. NOX4 mainly expressed at intracellular membranes, such as ER and mitochondria, which sole function is to produce ROS as the major product. At present, whether NOX4 is activated and the mechanisms between NOX4 and ER stress during the development of morphine tolerance still need to be confirmed. Here, our research, for the first time, demonstrated that chronic administration of morphine up-regulated the expression of NOX4 at spinal cord through activating the three ER stress sensors (PERK, IRE1, ATF6), and subsequently leading to the activation of LC3B and P62 (a well-known autophagy marker) in GABAergic neurons. Therefore, our results may suggest that regulating NOX4 and the key factor of ER stress or autophagy may be a promising strategy to treat and prevent the development of morphine tolerance.
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