Nicotine and menthol independently exert neuroprotective effects against cisplatin-or amyloid-toxicity by upregulating Bcl-xl via JNK activation in SH-SY5Y cells  

作　　者：YIBIN RUAN ZHONGMING XIE QIONG LIU LIXIAO ZHANG XIKUI HAN XIAOYAN LIAO JIAN LIU FENGGUANG GAO 

机构地区：[1]Technology Center,China Tobacco Guizhou Industrial Co.,Ltd.,Guiyang,550003,China [2]Department of Basic Medical Sciences,School of Medicine,Xiamen University,Xiamen,361102,China

出　　处：《BIOCELL》2021年第4期1059-1067,共9页生物细胞（英文）

基　　金：supported by the Young Elite Scientists Sponsorship Program of China Association for Science and Technology(No.2016QNRC001);the National Natural Science Foundation of China(Nos.81771669,81273203).

摘　　要：Nicotine and menthol,agonists of nicotinic acetylcholine receptor(nAChR)and transient receptor potential melastatin type 8(TRPM8),serve important roles in the prevention of cell death-involved neurodegenerative diseases.However,the potential synergistic effects of nicotine and menthol on anti-apoptotic ability are still uncertain.In the present study,the potential synergistic effects of nicotine and menthol on cisplatin or amyloidβ1-42 induced cell model of the neurodegenerative diseases were explored by assessing cell viability,TNF-αexpression,caspase-3 activation,and the collapse of mitochondrial membrane potential in human SH-SY5Y neuroblastoma cells.Statistical significance was tested using Student’s t-test or one-way ANOVA with post hoc Newman-Keuls test.The results showed that:Firstly,SH-SY5Y cell viability was obviously increased by the treatments with nicotine and menthol.Secondly,nicotine and menthol independently alleviated cisplatin or amyloidβ1-42 induced TNF-αup-regulation.Thirdly,nicotine and menthol abrogated the effect of cisplatin and amyloidβ25-35 on caspase-3 activation.Interestingly,the effect of cisplatin and amyloidβ1-42 on the collapse of mitochondrial membrane potential was efficiently attenuated by nicotine and menthol treatments.Most importantly,the inhibition of c-jun kinase(JNK)activation abolished the effect of cisplatin,and amyloidβ1-42 stimulated Bcl-xl expression.All these findings indicate that nicotine and menthol independently exert neuroprotective effects by upregulating Bcl-xl via JNK activation.Nicotine and menthol augmented Bcl-xl expression and JNK phosphorylation,and thus they are potential therapeutic targets for altering the progress of neurodegenerative diseases.

关 键 词：NICOTINE MENTHOL Apoptosis Mitochondrial membrane potential Tumor necrosis factor-alpha 

分 类 号：R73[医药卫生—肿瘤]