Abstract
The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA synthetic response of rat livers to toxic injury induced by a 350 or 800 mg/kg ip injection of galactosamine and that caused by 70% hepatectomy, comparing the changes in epidermal growth factor receptor status. Both resulted in down regulation of epidermal growth factor receptors, suggesting similar ligand epidermal growth factor receptor binding occurs during the proliferative response after galactosamine administration and after partial hepatectomy. In vitro studies on isolated hepatocytes showed that epidermal growth factor receptor down regulation was not a direct effect of galactosamine on hepatocyte membranes.
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- Alison M. R. Regulation of hepatic growth. Physiol Rev. 1986 Jul;66(3):499–541. doi: 10.1152/physrev.1986.66.3.499. [DOI] [PubMed] [Google Scholar]
- Aronson N. N., Jr, Touster O. Isolation of rat liver plasma membrane fragments in isotonic sucrose. Methods Enzymol. 1974;31:90–102. doi: 10.1016/0076-6879(74)31009-9. [DOI] [PubMed] [Google Scholar]
- Earp H. S., O'Keefe E. J. Epidermal growth factor receptor number decreases during rat liver regeneration. J Clin Invest. 1981 May;67(5):1580–1583. doi: 10.1172/JCI110190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Francavilla A., Ove P., Polimeno L., Sciascia C., Coetzee M. L., Starzl T. E. Epidermal growth factor and proliferation in rat hepatocytes in primary culture isolated at different times after partial hepatectomy. Cancer Res. 1986 Mar;46(3):1318–1323. [PMC free article] [PubMed] [Google Scholar]
- Gruppuso P. A., Mead J. E., Fausto N. Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat. Cancer Res. 1990 Mar 1;50(5):1464–1469. [PubMed] [Google Scholar]
- Keppler D., Decker K. Studies on the mechanism of galactosamine-1-phosphate and its inhibition of UDP-glucose pyrophosphorylase. Eur J Biochem. 1969 Sep;10(2):219–225. doi: 10.1111/j.1432-1033.1969.tb00677.x. [DOI] [PubMed] [Google Scholar]
- Keppler D., Lesch R., Reutter W., Decker K. Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol. 1968 Oct;9(2):279–290. doi: 10.1016/0014-4800(68)90042-7. [DOI] [PubMed] [Google Scholar]
- Marquardt H., Hunkapiller M. W., Hood L. E., Twardzik D. R., De Larco J. E., Stephenson J. R., Todaro G. J. Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4684–4688. doi: 10.1073/pnas.80.15.4684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Massagué J. Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells. J Biol Chem. 1983 Nov 25;258(22):13614–13620. [PubMed] [Google Scholar]
- Mead J. E., Fausto N. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558–1562. doi: 10.1073/pnas.86.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
- Munro H. N. The determination of nucleic acids. Methods Biochem Anal. 1966;14:113–176. doi: 10.1002/9780470110324.ch5. [DOI] [PubMed] [Google Scholar]
- Nakata R., Tsukamoto I., Miyoshi M., Kojo S. Liver regeneration after carbon tetrachloride intoxication in the rat. Biochem Pharmacol. 1985 Feb 15;34(4):586–588. doi: 10.1016/0006-2952(85)90195-9. [DOI] [PubMed] [Google Scholar]
- Okamoto M., Karasik A., White M. F., Kahn C. R. Epidermal growth factor stimulated phosphorylation of a 120-kilodalton endogenous substrate protein in rat hepatocytes. Biochemistry. 1990 Oct 9;29(40):9489–9494. doi: 10.1021/bi00492a023. [DOI] [PubMed] [Google Scholar]
- Rall L. B., Scott J., Bell G. I., Crawford R. J., Penschow J. D., Niall H. D., Coghlan J. P. Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues. Nature. 1985 Jan 17;313(5999):228–231. doi: 10.1038/313228a0. [DOI] [PubMed] [Google Scholar]
- Rubin R. A., O'Keefe E. J., Earp H. S. Alteration of epidermal growth factor-dependent phosphorylation during rat liver regeneration. Proc Natl Acad Sci U S A. 1982 Feb;79(3):776–780. doi: 10.1073/pnas.79.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato H., Sugiyama Y., Kim D. C., Yanai S., Kurita M., Fuwa T., Iga T., Hanano M. Decrease in the number of receptors for epidermal growth factor in the liver of D-galactosamine-intoxicated rats. Biochem Pharmacol. 1989 Aug 15;38(16):2663–2671. doi: 10.1016/0006-2952(89)90552-2. [DOI] [PubMed] [Google Scholar]
- Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
- Schacterle G. R., Pollack R. L. A simplified method for the quantitative assay of small amounts of protein in biologic material. Anal Biochem. 1973 Feb;51(2):654–655. doi: 10.1016/0003-2697(73)90523-x. [DOI] [PubMed] [Google Scholar]
- Selden C., Hodgson H. J. Further characterisation of 'hepatotropin', a high molecular weight hepatotrophic factor in rat serum. J Hepatol. 1989 Sep;9(2):167–176. doi: 10.1016/0168-8278(89)90047-0. [DOI] [PubMed] [Google Scholar]
- Selden C., Jones M., Wade D., Hodgson H. Hepatotropin mRNA expression in human foetal liver development and in liver regeneration. FEBS Lett. 1990 Sep 17;270(1-2):81–84. doi: 10.1016/0014-5793(90)81239-k. [DOI] [PubMed] [Google Scholar]
- Vesey D. A., Cunningham J. M., Selden A. C., Woodman A. C., Hodgson H. J. Dimethyl sulphoxide induces a reduced growth rate, altered cell morphology and increased epidermal-growth-factor binding in Hep G2 cells. Biochem J. 1991 Aug 1;277(Pt 3):773–777. doi: 10.1042/bj2770773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wollenberg G. K., Harris L., Farber E., Hayes M. A. Inverse relationship between epidermal growth factor induced proliferation and expression of high affinity surface epidermal growth factor receptors in rat hepatocytes. Lab Invest. 1989 Feb;60(2):254–259. [PubMed] [Google Scholar]

