INVOLVEMENT OF P42/44 MAPK IN THE EFFECTS OF ETHANOL ON SECRETION OF INSULIN-LIKE GROWTH FACTOR (IGF)-I AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP)-1 IN PRIMARY CULTURED RAT HEPATOCYTES

Abstract

This article investigates the effects of ethanol on Insulin-like growth factor (IGF)-I secretion, p42/44 mitogen-activated protein kinase (MAPK) activity, and IGF binding protein (IGFBP-1 secretion) in primary cultured rat hepatocytes. The p42/44 MAPK activity increased with the ethanol concentration compared to control after ethanol treatment. The secretion of IGF-I significantly increased compared to control, but IGFBP-1 secretion was inhibited. Treatment with 4-methylpyrazole blocked the IGF-I and IGFBP-1 secretion and p42/44 MAPK activity. Increased IGF-I secretion and inhibited IGFBP-1 secretion due to ethanol-induced p42/44 MAPK activity (at 30 min) was blocked by treatment with PD98059. Taken together, these results suggest that ethanol is involved in the modulation of the secretion of IGF-I and IGFBP-1 by p42/44 MAPK in primary cultured rat hepatocytes. In addition, inhibition of p42/44 MAPK activity by ethanol occurs via the activity of ADH.

Key Words:

• ethanol
• IGF-I
• IGFBP-1
• p42/44 MAPK