Protective effect of insulin-like-growth-factor-1 against dopamine-induced neurotoxicity in human and rodent neuronal cultures: possible implications for Parkinson's disease.
Parkinson's disease (PD) is characterized by a progressive loss of 70-80% of dopaminergic (DA) neurons in the substantia nigra. High concentrations of DA were suggested to induce oxidative stress and selective neurodegeneration. We evaluated the effect of insulin-like-growth-factor-1 (IGF-1) on DA toxicity in neuronal cultures. IGF-1 (0.5 microg/ml) suppressed cell death induced by exposure to DA (0.3 mM) after 2 and 4 days, in a rat cerebellar culture. Similarly, IGF-1 (0.5 and 1.0 microg/ml) antagonized DA (0.125 and 0.250 mM) neurotoxicity in a human neuroblastoma cell line (SK-N-SH). Flowcytometric analysis of neuroblastoma cells treated with DA (0.5 mM) showed increased apoptosis, which was significantly reduced by IGF-1. The effect of IGF-1 was associated with increased Bcl-2 expression as indicated by flowcytometry and Western blot analysis. We suggest that IGF-1 possesses a neuroprotective effect against DA-induced toxicity, and may have a potential role in the treatment of PD.
Offen
D
D
Neurosciences Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Tel Aviv University Sackler School of Medicine, Petah Tikva, 49100 Israel. doffen@post.tau.ac.il
Shtaif
B
B
Hadad
D
D
Weizman
A
A
Melamed
E
E
Gil-Ad
I
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex; D004298:Dopamine / Q000378:metabolism* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D018696:Neuroprotective Agents; D009498:Neurotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D007334:Insulin-Like Growth Factor I; D004298:Dopamine