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

[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 amyloid β 1-42 induced cell model of the neurodegenerative diseases were explored by assessing cell viability, TNF-α expression, 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 amyloid β 1-42 induced TNF-α up-regulation. Thirdly, nicotine and menthol abrogated the effect of cisplatin and amyloid β 25-35 on caspase-3 activation. Interestingly, the effect of cisplatin and amyloid β 1-42 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 amyloid β 1-42 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.

[学科分类] 仪器

[关键词] Nicotine;Menthol;Apoptosis;Mitochondrial membrane potential;Tumor necrosis factor-alpha