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

We have previously shown that insulin and the insulin-like growth factors 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 of 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 curves for these increases were very similar to that for enhancement of neurite formation. Tubulin transcripts reached a transient maximum in approximately 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 mechanisms 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 coordinate increase in actin and tubulin transcripts in SH-SY5Y cells.