Inhibition of insulin-like growth factor-1 receptor and IRS-2 signaling byethanol in SH-SY5Y neuroblastoma cells

The effect of ethanol on insulin-like growth factor-1 (IGF-I)-mediated sign al transduction and functional activation in neuronal cells was examined. I n human SH-SY5Y neuroblastoma cells, ethanol inhibited tyrosine autophospho rylation of the IGF-I receptor. This corresponded to the inhibition of IGF- I-induced phosphorylation of p42/p44 mitogen-activated/extracellular signal -regulated protein kinase (MAPK) by ethanol. Insulin-related substrate-2 (I RS-2) and focal adhesion kinase phosphorylation were reduced in the presenc e of ethanol, which corresponded to the prevention of lamellipodia formatio n (30 min). By contrast, ethanol had no effect on Shc phosphorylation when measured up to 1 h, and did not affect the association of Grb-2 with Shc. N eurite formation at 24 h was similarly unaffected by ethanol. The data indi cate that the IGF-I receptor is a target for ethanol in SH-SY5Y cells Howev er, there is diversity in the sensitivity of signaling elements within the IGF-I receptor tyrosine kinase signaling cascades to ethanol, which can be related to the inhibition of specific functional events in neuronal activat ion.