Leptin inhibits 1-methyl-4-phenylpyridinium-induced cell death in SH-SY5Y cells

Leptin is best known as a key satiety factor and it is now appreciated that leptin has many additional biological functions. Our previous study suggested that leptin-resistant obesity might exacerbate 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in vivo. Here, we ask whether leptin might protect neuronal cells against 1-methyl-4-pyridinium (MPP+)-induced cell death. We used differentiated SH-SY5Y cells and investigated plausible cytoprotective signalling mechanisms. When SH-SY5Y cells were maintained under serum-free conditions for 48 h, MPP+ (1 mM) reduced cell viability to 66.8% of the drug-free control, and leptin significantly inhibited cell death in a dose-dependent manner. Among inhibitors of known leptin signalling pathways, a PI-3K inhibitor inhibited the protective effect of leptin during MPP+ exposure, whereas inhibitors affecting the Janus kinase/signal transducers and activators of transcription (JAK/STAT) or mitogen-activated protein kinase (MAPK) pathways did not influence cell viability. We used immunoblotting to show that the PI-3K/Akt pathway was involved in the effect of leptin on cell viability. In conclusion, our results show that leptin exercises a cytoprotective effect against MPP+-induced cell death and that this effect is dependent on activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in SH-SY5Y cells. The data tend to support our previous results in vivo.