Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation.

Abstract

We have previously shown that insulin and the insulin-like growth factos share some important neurotrophic properties with nerve growth factor (NGF), including the capacity to enhance neurite formation. In this study, we have examined the effects of these neuritogenic agents on the expression of genes coding for important cytoskeletal proteins or axons and dendrites. Insulin specifically and coordinately increased the levels of .alpha.- and .beta.-tubulin mRNAs in human neuroblastoma SH-SY5Y cells. The dose-response ceruves for these increases were very similar to that for enhancement of neurite formation. Tubulin transcripts reached a transient maximum in .apprxeq. 1 day, suggesting that higher levels are important during initiation of neurites and that high levels are not required to sustain neurites once formed. Insulin-like growth factor II shared with insulin the capacity to substantially increase tubulin mRNA levels. NGF had but a small effect. Complementary mecahnisms for these neurotrophic agents are suggested, because other studies show NGF and insulin can synergistically potentiate neurite formation. None of the factors altered the levels of actin mRNA. Thus, neurite formation does not seem to require a corrdinate increase in actin and tubulin transcripts in SH-SY5Y cells.