Insulin-like growth factor binding protein 5 and type-1 insulin-like growth factor receptor are differentially regulated during apoptosis in cerebellar granule cells

Neuronal apoptosis is considered to play a significant role in several neur opathological conditions. However, the molecular mechanisms underlying neur onal apoptosis are poorly understood. Insulin-like growth factor (IGF) sign alling is considered to be an important regulator of neuronal differentiati on, survival and apoptosis. We have examined the expression of two members of the IGF system, insulin-like growth factor binding protein 5 (IGFBP-5) a nd the type-1 IGF receptor (IGF1R), during apoptosis of rat cerebellar gran ule cells (CGCs) in vitro. We describe a prominent downregulation of IGFBP- 5 mRNA and protein expression. We also show that IGF-I increases IGFBP-5 ex pression in CGCs and that the downregulation of IGFBP-5 mRNA can be suppres sed by inhibiting mRNA synthesis with actinomycin D. The expression of IGF1 R mRNA showed a transient upregulation during potassium chloride (KCl) depr ivation induced apoptosis, in contrast to the IGF1R protein level, which wa s downregulated during KCl deprivation. Our results provide insight into th e expression of IGF-related genes during neuronal apoptosis, and indicate t hat they mediate a protective response to the withdrawal of trophic stimula tion. It seems that the expression of IGFBP-5 and IGF1R is regulated to max imize the availability of IGF and the activity of IGF-triggered survival si gnalling.