Prevention of apoptosis by insulin-like growth factor (IGF)-I and IGF-II is differentially attenuated by IGF-binding proteins in PC12 cells

The insulin-like growth factor (IGF) system plays a prominent role in the n ervous system. To determine the potential role of IGF-binding proteins (IGF BPs) in modulating the survival promoting actions of IGF-I and IGF-II in ne uronal cell systems we have utilised the PC12 cell model of serum deprivati on-induced apoptosis. IGFBP-2 effectively prevented both IGF-I- and IGF-LI- induced survival, whereas IGFBP-6 specifically attenuated IGF-II-induced PC 12 cell survival. IGFBP-1 was less effective at preventing IGF survival res ponses. In contrast, IGF analogs with reduced affinity for IGFBPs maintaine d their ability to prevent serum-deprivation induced apoptosis in the prese nce of each IGFBP indicating that IGFBPs inhibit IGF-induced PC12 cell surv ival by directly sequestering IGFs thus preventing their binding to the typ e I IGF receptor. These results suggest that IGFBPs may act as important ne gative regulators of the neurotrophic actions of IGFs.