食品科学2025，Vol.46Issue(9)：1-10,10.DOI:10.7506/spkx1002-6630-20240913-102
肉豆蔻木酚素通过PI3K/Akt信号通路调节HT22细胞自噬和凋亡的作用机制
Regulatory Mechanism of Macelignan on Autophagy and Apoptosis of HT22 Cells via PI3K/Akt Signaling Pathway
摘要
Abstract
To explore the regulatory mechanism of the natural compound macelignan on apoptosis and autophagy in hippocampal neurons,this study investigated the effect of macelignan on the survival rate of HT22 cell line under glutamate-induced oxidative stress.Morphological changes and apoptosis were assessed by hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase(TDT)-mediated dUTP nick-end labeling(TUNEL)staining and flow cytometry.The binding of macelignan with phosphatidylinositide 3-kinase(PI3K)was analyzed by molecular docking.Western blot was used to analyze the effects of macrolignan combined with the PI3K inhibitor Ly294002 or the autophagy inhibitor 3-methyladenine(3-MA)on the protein expression levels of PI3K and protein kinase B(Akt),as well as apoptosis and autophagy-related proteins such as cleaved caspase-3,microtubule-associated protein light chain 3 beta(LC3B),and autophagy related gene 5(Atg5).The results demonstrated that macelignan promoted HT22 cell viability and suppressed apoptosis in a concentration-dependent manner.It could enhance the phosphorylation of p-PI3K and p-Akt,inhibit the expression of cleaved caspase-3,and exert an anti-apoptotic effect via the PI3K/Akt signaling pathway.Meanwhile,it could inhibit autophagy by reducing the expression of Atg5 and LC3B and increasing the level of p62.Ly294002 could block the promoting effect of macelignan on the phosphorylation of PI3K and Akt,while 3-MA could enhance its neuroprotective effect.In conclusion,macelignan exerts a neuroprotective effect through activating the PI3K/Akt signaling pathway,inhibiting autophagy and attenuating glutamate-induced apoptosis in HT22 cells.关键词
肉豆蔻木酚素/谷氨酸/神经退行性疾病/凋亡/自噬Key words
macelignan/glutamate/neurodegenerative diseases/apoptosis/autophagy分类
轻工业引用本文复制引用
齐正宇,邱新茹,楚新歌,李莎,延光海,崔春爱..肉豆蔻木酚素通过PI3K/Akt信号通路调节HT22细胞自噬和凋亡的作用机制[J].食品科学,2025,46(9):1-10,10.基金项目
国家自然科学基金地区科学基金项目(82060746 （）
81660687)吉林省科技发展计划项目(YDZJ202501ZYTS235) （YDZJ202501ZYTS235）
