Neuroprotective effect of insulin-like growth factor I in immortalized hypothalamic cells.
The neuroprotective action of insulin-like growth factor I (IGF-I) was tested in immortalized hypothalamic GT1-7 cells exposed to reduced glutathione depleting agents, which cause oxidative stress and cell death. The extent of cell survival was assessed by either using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay or counting at the fluorescence microscope GT1-7 cells prelabeled with fluorescent dyes selective for viable and dead cells. Treatments with buthionine sulfoximine (500 microns), diethylmaleate (1 mM), and ethacrynic acid (200 microns) caused diffuse GT1-7 cell death (40-60%). Exposure of the same cells to IGF-I (either before or concomitant to the toxic agent, depending on the drug used) significantly prevented neuronal death. This effect was rapid, concentration-dependent, maximal at concentrations of 25-50 ng/ml, and mimicked by IGF-II, fibroblast growth factor, and the potent antioxidant idebenone. In contrast, IGF-I, as well as idebenone, were completely ineffective in antagonizing the toxic effect produced by different concentrations of menadione. In conclusion, the present data demonstrate a protective role for IGF-I against glutathione depleting agents-induced damage in GT1-7 cells suggesting an antioxidant action of this growth factor in hypothalamic neurons.
Sortino
M A
MA
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Canonico
P L
PL
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D016923:Cell Death; D002461:Cell Line, Transformed; D004976:Ethacrynic Acid / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008298:Maleates / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives; D014812:Vitamin K / Q000494:pharmacology
D016227:Benzoquinones; D008298:Maleates; D018696:Neuroprotective Agents; D011837:Radiation-Protective Agents; D014812:Vitamin K; D014451:Ubiquinone; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D007334:Insulin-Like Growth Factor I; C014476:diethyl maleate; C036619:idebenone; D004976:Ethacrynic Acid