title: Relationship between the neuroprotective effects of insulin-like growth factor-1 and 17β-oestradiol in human neuroblasts.
abstract: Insulin-like growth factor-1 (IGF-1) and oestrogens interact with each other as neuroprotective factors. We have previously demonstrated that 17β-oestradiol protects against β-amyloid and oxidative stress toxicity and increases the amount of cell cholesterol in human foetal neuroblasts (FNC). The present study aimed: (i) to assess the protective effects of IGF-1 in FNC cells; (ii) to investigate the relationship between IGF-1 and 17β-oestradiol; and (iii) to determine whether cholesterol was a major mediator of the effects of IGF-1, similarly to 17β-oestradiol. We found that IGF-1 effectively exerts neuroprotective effects in FNC cells. We also demonstrated that the IGF-1 receptor (IGF-1R) pathway is needed to maintain oestrogen-mediated neuroprotection. Finally, we found that, opposite to 17β-oestradiol, IGF-1 did not cause a significant increase in cell cholesterol. These findings indicate that a cross-talk between IGF-1 and 17β-oestradiol occurs in FNC cells. In particular, the activation of the IGF-1R cascade appears to be fundamental to warrant 17β-oestradiol-mediated neuroprotection, even though cell cholesterol does not play a major role as an effector of this pathway.
authors.affiliation: Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies-DENOThe, University of Florence, Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Luciani
authors.forename: C
authors.initials: C
authors.lastname: Deledda
authors.forename: S
authors.initials: S
authors.lastname: Benvenuti
authors.forename: I
authors.initials: I
authors.lastname: Cellai
authors.forename: G
authors.initials: G
authors.lastname: Modi
authors.forename: B
authors.initials: B
authors.lastname: Fibbi
authors.forename: G
authors.initials: G
authors.lastname: Danza
authors.forename: G B
authors.initials: GB
authors.lastname: Vannelli
authors.forename: A
authors.initials: A
authors.lastname: Peri
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol