Chronic Ethanol Consumption Disrupts Complexation between EGF Receptor and Phospholipase C-γ1: Relevance to Impaired Hepatocyte Proliferation

Hepatocyte Proliferation is the Possible Mechanism for the Transient Decrease in Liver Injury During Steatosis Stage of Alcoholic Liver Disease

“…While there are reports to suggest an impaired regenerative response in EtOH-treated rodents following partial hepatectomy (Zhang and Farrell, 1999;Diehl, 1999;Koteish et al, 2002;Phillips et al, 2002) and chemical-induced liver injury (Chen et al, 1998, Diehl, 1999Diehl, 2002b;Koteish et al, 2002), other studies including the present study suggest enhancement in liver regeneration. The conflicting reports may be attributed to the time and dose dependent nature of liver regeneration.…”

HC fragment (C-terminal portion of the heavy chain) of tetanus toxin activates protein kinase C isoforms and phosphoproteins involved in signal transduction

“…Thus the modest increase in polyphosphoinositide hydrolysis in synaptosomes by NGF and TeTx described by our group, when compared with the muscarinic agonist carbachol [11,29], can be related to isoformspecific PLC activation. On the other hand, PLCγ-1 translocation has been described in several studies, and this event has been related to its phosphotyrosine content and to the activation of tyrosine kinase receptors [31]. In addition to the probable role of PLCγ-1 in TeTx-triggered pathways, the H C -TeTx-induced phosphorylation of trkA in Tyr%*!…”

Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors

“…Moreover, ethanol exerts differential effect on the same growth factor depending on the cell type. Although ethanol inhibits the signaling events by EGF in hepatocytes (Higashi and Hoek, 1991;Saso et al, 1997;Zhang and Farrell, 1999), ethanol did not directly interfere with EGF receptor function in mouse BALB/c3T3 cells (Resnicoff et al, 1996). Ethanol inhibited the proliferation of PDGF-stimulated astrocyte, but some studies could not show the inhibitory effect of ethanol on PDGF-induced increases in cell proliferation (Resnicoff et al, 1994;Guizetti and Costa, 1996) and in DNA synthesis (Tomono and Kiss, 1995;DeVito et al, 1997).…”

“…Ethanol might activate those signaling proteins by a pertussis toxinsensitive G-protein-dependent mechanism (Reddy and Shukla, 1996). In most cases, ethanol inhibits growth factor-induced receptor tyrosine autophosphorylation (Thurston, Jr. and Shukla, 1992;Resnicoff et al, 1993Resnicoff et al, , 1994Bhavani et al, 1995), which subsequently interferes with the activation of key down stream signaling mediators including PLC-g1 (Higashi and Hoek, 1991;Thurston, Jr. and Shukla, 1992;Saso et al, 1997;Zhang and Farrell, 1999), IRS-1 (Resnicoff et al, 1994;Bhavani et al, 1995), phosphatidylinositol-3 kinase (Resnicoff et al, 1994), and MAP kinases (Banerjee et al, 1998;Thombes et al, 1998;Seiler et al, 2000), and transcription factors such as c-myc, c-fos, and c-jun (Resnicoff et al, 1993). We also observed an inhibition of EGF-or PDGF-stimulated ERK activity.…”

“…The blockage of growth factor-mediated cell proliferation by ethanol in several systems elicits the hypothesis that growth factor-induced signaling processes are targets of ethanol toxicity. Included are adenylate cyclase (Hoek et al, 1992;Williams and Kelly, 1993), protein kinase C (Pandy, 1996), protein tyrosine kinases (Miyakawa et al, 1997, Resnicoff et al, 1993, Thurston and Shukla, 1992, MAPKs (Roivainen et al, 1995;Reddy and Shukla, 1996;Chen et al, 1998;Tombes et al, 1998;Reddy and Shukla, 2000), phospholipase C and D (Higashi and Hoek, 1991;Hoek et al, 1992;Thurston and Shukla, 1992;Saso et al, 1997;Zhang and Farrell, 1999), transcription factors such as NF-κB (Zeldin et al, 1996) and STAT3 (Chen et al, 1997).…”