Altered Levels of Prothymosin Immunoreactive Peptide, a Growth‐Related Gene Product, During Liver Regeneration after Chronic Ethanol Feeding

Abstract

Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several proto-oncogenes, including c-myc, which peaks 3-6 hr post-partial hepatectomy. Prothymosin alpha, a gene encoding a ubiquitous nuclear protein, is activated by c-myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin alpha mRNA levels reportedly increase 12-32 hr post-partial hepatectomy, several hours after c-myc induction. We sought to determine if chronic ethanol intake alters the expected induction post-partial hepatectomy of prothymosin alpha steady-state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair-fed controls, we found no significant differences in steady-state levels of prothymosin alpha mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady-state mRNA levels, but may occur post-transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.

Proliferation-inhibiting pathways in liver regeneration

“…Prolonging of the activation of p42/44 MAPK and decreased expression of γ-aminobutyric acid transport protein are also involved in the damaged proliferation of hepatocytes (158,159). By contrast, prothymosin-α, p38 MAPK and p21 are associated with impaired liver regeneration following chronic ethanol administration (158,160,161).…”

Prothymosin α Functions as a Cellular Oncoprotein by Inducing Transformation of Rodent Fibroblasts in Vitro

“…This relationship has been supported by the direct correlation of both ProT␣ mRNA and protein levels with levels of proliferation. The transcript is induced upon growth stimulation of resting lymphocytes (4), thymocytes (10), NIH 3T3 fibroblasts (4,11), and hepatocytes during liver regeneration (10,12). Moreover, ProT␣ concentrations were reported to be higher in tumor samples than in normal breast tissue (13), and were phosphorylated in stimulated proliferating cells (14).…”