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 gl utathione depleting agents, which cause oxidative stress and cell deat h. The extent of cell survival was assessed by either using the [4,5-d imethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assa y or counting at the fluorescence microscope GT1-7 cells prelabeled wi th fluorescent dyes selective for viable and dead cells. Treatments wi th buthionine sulfoximine (500 mu M), diethylmaleate (1 mM), and ethac rynic acid (200 mu M) caused diffuse GT1-7 cell death (40-60%). Exposu re of the same cells to IGF-I (either before or concomitant to the tox ic agent, depending on the drug used) significantly prevented neuronal death. This effect was rapid, concentration-dependent, maximal at con centrations of 25-50 ng/ml, and mimicked by IGF-II, fibroblast growth factor, and the potent antioxidant idebenone. In contrast, IGF-I, as w ell as idebenone, were completely ineffective in antagonizing the toxi c effect produced by different concentrations of menadione. In conclus ion, 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.