Insulin-like growth factor-1 protects human dopaminergic SH-SY5Y cells from salsolinol-induced toxicity.
Parkinson's disease (PD) is characterized by an extensive loss of dopaminergic neurons in the substantia nigra pars compacta. Salsolinol (SAL), a dopamine-derived tetrahydroisoquinoline, has been suspected to be involved in the etiology of PD. In the present study, the neuroprotective effect of insulin-like growth factor-1 (IGF-1) was studied against SAL-induced toxicity in human dopaminergic SH-SY5Y cells. SAL (100 microM) decreased cell viability in SH-SY5Y cells significantly after 24 h exposure. Both exogenous IGF-1 and IGF-1 gene transfer significantly prevented the SAL-induced cell death and increased cell viability. Wortmannin, a specific phosphatidylinositol-3-kinase (PI-3 kinase) inhibitor, completely blunted the IGF-1-induced neuroprotection, suggesting that PI-3 kinase pathway is critical in mediating the neuroprotective effects of IGF-1. These results suggest that IGF-1 may be a useful growth factor in the treatment of PD.
Shavali
Shaik
S
Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, ND 58203, USA.
Ren
Jun
J
Ebadi
Manuchair
M
D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology*; D007546:Isoquinolines / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D007546:Isoquinolines; D007334:Insulin-Like Growth Factor I; C036617:salsolinol; D004298:Dopamine