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. 1995 Sep;147(3):699–706.

Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy.

R P Evarts 1, Z Hu 1, N Omori 1, M Omori 1, E R Marsden 1, S S Thorgeirsson 1
PMCID: PMC1870991  PMID: 7677181

Abstract

The effect of vitamin A deficiency on hepatic regeneration in male and female rats was studied after partial hepatectomy. A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate 1 hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats. The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-beta 1 were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged. Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. doi: 10.1016/0304-419x(91)90011-9. [DOI] [PubMed] [Google Scholar]
  2. Blackwood E. M., Lüscher B., Eisenman R. N. Myc and Max associate in vivo. Genes Dev. 1992 Jan;6(1):71–80. doi: 10.1101/gad.6.1.71. [DOI] [PubMed] [Google Scholar]
  3. Bursch W., Oberhammer F., Jirtle R. L., Askari M., Sedivy R., Grasl-Kraupp B., Purchio A. F., Schulte-Hermann R. Transforming growth factor-beta 1 as a signal for induction of cell death by apoptosis. Br J Cancer. 1993 Mar;67(3):531–536. doi: 10.1038/bjc.1993.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buttke T. M., Sandstrom P. A. Oxidative stress as a mediator of apoptosis. Immunol Today. 1994 Jan;15(1):7–10. doi: 10.1016/0167-5699(94)90018-3. [DOI] [PubMed] [Google Scholar]
  5. Carson W. E., Haldar S., Baiocchi R. A., Croce C. M., Caligiuri M. A. The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7553–7557. doi: 10.1073/pnas.91.16.7553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clarke A. R., Purdie C. A., Harrison D. J., Morris R. G., Bird C. C., Hooper M. L., Wyllie A. H. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature. 1993 Apr 29;362(6423):849–852. doi: 10.1038/362849a0. [DOI] [PubMed] [Google Scholar]
  7. Colombel M., Olsson C. A., Ng P. Y., Buttyan R. Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle. Cancer Res. 1992 Aug 15;52(16):4313–4319. [PubMed] [Google Scholar]
  8. Colotta F., Polentarutti N., Sironi M., Mantovani A. Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines. J Biol Chem. 1992 Sep 15;267(26):18278–18283. [PubMed] [Google Scholar]
  9. Cáceres-Cortés J., Rajotte D., Dumouchel J., Haddad P., Hoang T. Product of the steel locus suppresses apoptosis in hemopoietic cells. Comparison with pathways activated by granulocyte macrophage colony-stimulating factor. J Biol Chem. 1994 Apr 22;269(16):12084–12091. [PubMed] [Google Scholar]
  10. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  11. Fujio K., Evarts R. P., Hu Z., Marsden E. R., Thorgeirsson S. S. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab Invest. 1994 Apr;70(4):511–516. [PubMed] [Google Scholar]
  12. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  14. Gold R., Schmied M., Giegerich G., Breitschopf H., Hartung H. P., Toyka K. V., Lassmann H. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques. Lab Invest. 1994 Aug;71(2):219–225. [PubMed] [Google Scholar]
  15. Goldstone S. D., Lavin M. F. Prolonged expression of c-jun and associated activity of the transcription factor AP-1, during apoptosis in a human leukaemic cell line. Oncogene. 1994 Aug;9(8):2305–2311. [PubMed] [Google Scholar]
  16. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hockenbery D. M., Oltvai Z. N., Yin X. M., Milliman C. L., Korsmeyer S. J. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993 Oct 22;75(2):241–251. doi: 10.1016/0092-8674(93)80066-n. [DOI] [PubMed] [Google Scholar]
  18. Hu Z., Fujio K., Marsden E. R., Thorgeirsson S. S., Evarts R. P. Hepatic regeneration in vitamin A-deficient rats: changes in the expression of transforming growth factor alpha/epidermal growth factor receptor and retinoic acid receptors alpha and beta. Cell Growth Differ. 1994 May;5(5):503–508. [PubMed] [Google Scholar]
  19. Iemura A., Tsai M., Ando A., Wershil B. K., Galli S. J. The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol. 1994 Feb;144(2):321–328. [PMC free article] [PubMed] [Google Scholar]
  20. Kastan M. B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed] [Google Scholar]
  21. Kerr J. F., Winterford C. M., Harmon B. V. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994 Apr 15;73(8):2013–2026. doi: 10.1002/1097-0142(19940415)73:8<2013::aid-cncr2820730802>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  22. Kyprianou N., Isaacs J. T. Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Mol Endocrinol. 1989 Oct;3(10):1515–1522. doi: 10.1210/mend-3-10-1515. [DOI] [PubMed] [Google Scholar]
  23. Lowe S. W., Schmitt E. M., Smith S. W., Osborne B. A., Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993 Apr 29;362(6423):847–849. doi: 10.1038/362847a0. [DOI] [PubMed] [Google Scholar]
  24. Muta K., Krantz S. B. Apoptosis of human erythroid colony-forming cells is decreased by stem cell factor and insulin-like growth factor I as well as erythropoietin. J Cell Physiol. 1993 Aug;156(2):264–271. doi: 10.1002/jcp.1041560207. [DOI] [PubMed] [Google Scholar]
  25. Peitsch M. C., Polzar B., Stephan H., Crompton T., MacDonald H. R., Mannherz H. G., Tschopp J. Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). EMBO J. 1993 Jan;12(1):371–377. doi: 10.1002/j.1460-2075.1993.tb05666.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  27. Rotello R. J., Lieberman R. C., Purchio A. F., Gerschenson L. E. Coordinated regulation of apoptosis and cell proliferation by transforming growth factor beta 1 in cultured uterine epithelial cells. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3412–3415. doi: 10.1073/pnas.88.8.3412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rubin E., Kharbanda S., Gunji H., Kufe D. Activation of the c-jun protooncogene in human myeloid leukemia cells treated with etoposide. Mol Pharmacol. 1991 Jun;39(6):697–701. [PubMed] [Google Scholar]
  29. Schwartzman R. A., Cidlowski J. A. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev. 1993 Apr;14(2):133–151. doi: 10.1210/edrv-14-2-133. [DOI] [PubMed] [Google Scholar]
  30. Shi Y. F., Bissonnette R. P., Parfrey N., Szalay M., Kubo R. T., Green D. R. In vivo administration of monoclonal antibodies to the CD3 T cell receptor complex induces cell death (apoptosis) in immature thymocytes. J Immunol. 1991 May 15;146(10):3340–3346. [PubMed] [Google Scholar]
  31. Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
  32. Tsuchiya M., Scita G., Freisleben H. J., Kagan V. E., Packer L. Antioxidant radical-scavenging activity of carotenoids and retinoids compared to alpha-tocopherol. Methods Enzymol. 1992;213:460–472. doi: 10.1016/0076-6879(92)13148-q. [DOI] [PubMed] [Google Scholar]
  33. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  34. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
  35. Yang Y., Vacchio M. S., Ashwell J. D. 9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6170–6174. doi: 10.1073/pnas.90.13.6170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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