Effect of ethanol on p36 protein kinase substrate and insulin receptor substrate 1 expression and tyrosyl phosphorylation in human hepatocellular carcinoma cells

Alcoholism, Clinical and Experimental Research
K BhavaniJ R Wands

Abstract

Ethanol inhibits insulin (IN) and epidermal growth factor (EGF)-induced hepatocyte DNA synthesis. Growth factor receptor kinases, such as IN and EGF, phosphorylate insulin receptor substrate (IRS-1) and p36 protein kinase substrate, respectively, on tyrosine residues. IRS-1 and p36 are thought to be important intracellular signal transduction molecules involved in the regulation of cell growth. These investigations explored the effect of ethanol additions on the expression and tyrosyl phosphorylation (TP) of p36 and IRS-1 in a human hepatocellular carcinoma cell line (FOCUS) in relationship to cell proliferation induced by IN and serum growth factor stimulation. It was found that p36 was constitutively and highly expressed in serum-starved cells and protein, and mRNA levels did not change with cell proliferation induced by growth factors. However, exposure of FOCUS cells to ethanol additions substantially inhibited TP of p36. The early TP of IRS-1 induced by IN stimulation was also reduced by ethanol additions. Finally, there was a parallel decrease of FOCUS cell proliferation in ethanol-exposed cultures. These studies suggest that one possible mechanism of ethanol inhibitory effect on cell proliferation is through reduced TP o...Continue Reading

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Citations

May 15, 1998·Alcoholism, Clinical and Experimental Research·M L AikensF M Booyse
Jul 11, 1998·Alcoholism, Clinical and Experimental Research·H E GrenettF M Booyse
Jun 17, 1999·Alcoholism, Clinical and Experimental Research·S M de la MonteJ R Wands
Mar 4, 2000·Alcoholism, Clinical and Experimental Research·A E SeilerR Rubin
Mar 4, 2015·Journal of Gastroenterology·Hirokazu TakahashiYuichiro Eguchi
May 23, 2015·Annals of the New York Academy of Sciences·Rotonya M Carr, Jason Correnti
Apr 3, 2003·Biochemical and Biophysical Research Communications·Yukiko OnishiTomoichiro Asano
Jul 7, 2011·Journal of Hematology & Oncology·Jennifer Wu, Andrew X Zhu
May 3, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Katherine A RadekLuisa A Dipietro
Nov 1, 1996·Alcoholism, Clinical and Experimental Research·L E Nagy
Mar 20, 2008·World Journal of Gastroenterology : WJG·Kai Breuhahn, Peter Schirmacher
Nov 30, 2000·American Journal of Physiology. Endocrinology and Metabolism·B YuL E Nagy

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