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.
Lu
Jingnan
J
Department of Pharmacology, Medicinal Toxicology Research Center, College of Medicine, Inha Research Institute for Medical Sciences, Inha University, Shinheungdong, Jung-Gu, Incheon, South Korea.
Park
Chang-Shin
CS
Lee
Sung-Keun
SK
Shin
Dong Wun
DW
Kang
Ju-Hee
JH
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor / Q000378:metabolism
D016895:Culture Media, Serum-Free; C515448:LEPR protein, human; D020738:Leptin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053614:Janus Kinase 2; D015655:1-Methyl-4-phenylpyridinium