MAPK/ERK通路
赖氨酰氧化酶
细胞生物学
脂质过氧化
激酶
神经科学
程序性细胞死亡
NADPH氧化酶
化学
癌症研究
生物
氧化应激
活性氧
生物化学
细胞凋亡
细胞外基质
作者
Xiao‐Yuan Mao,Xuan Wang,Mingzhu Jin,Qin Li,Ji-Ning Jia,Menghuan Li,Hong‐Hao Zhou,Zhao‐Qian Liu,Weilin Jin,Yanli Zhao,Zhong Luo
标识
DOI:10.1016/j.apsb.2022.04.017
摘要
Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.
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