Prevention of apoptosis by insulin-like growth factor (IGF)-I and IGF-II is differentially attenuated by IGF-binding proteins in PC12 cells
- Resource Type
- Article
- Authors
- Hale, Kate; Murray, Andrew W.; Cosgrove, Leah J.; Bach, Leon A.; Hartfield, Perry J.
- Source
- Neuroscience Research Communications; July/August 2000, Vol. 27 Issue: 1 p75-83, 9p
- Subject
- Language
- ISSN
- 08936609; 15206769
The insulin-like growth factor (IGF) system plays a prominent role in the nervous system. To determine the potential role of IGF-binding proteins (IGFBPs) in modulating the survival promoting actions of IGF-I and IGF-II in neuronal cell systems we have utilised the PC12 cell model of serum deprivation-induced apoptosis. IGFBP-2 effectively prevented both IGF-I- and IGF-II-induced survival, whereas IGFBP-6 specifically attenuated IGF-II-induced PC12 cell survival. IGFBP-1 was less effective at preventing IGF survival responses. In contrast, IGF analogs with reduced affinity for IGFBPs maintained their ability to prevent serum-deprivation induced apoptosis in the presence of each IGFBP indicating that IGFBPs inhibit IGF-induced PC12 cell survival by directly sequestering IGFs thus preventing their binding to the type I IGF receptor. These results suggest that IGFBPs may act as important negative regulators of the neurotrophic actions of IGFs.