Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1983 Aug 15;214(2):503–509. doi: 10.1042/bj2140503

Haematoporphyrin and OO'-diacetylhaematoporphyrin binding by serum and cellular proteins. Implications for the clearance of these photochemotherapeutic agents by cells.

A Smith, T Neuschatz
PMCID: PMC1152273  PMID: 6225429

Abstract

Haematoporphyrin derivative (HpD), a mixture of porphyrins, is currently used as a photochemotherapeutic agent in the treatment of neoplasias. The interaction of purified components of HpD with serum and cellular proteins was investigated using absorption and fluorescence spectroscopy. The interactions of haematoporphyrin and OO'-diacetylhaematoporphyrin with human albumin and with haemopexin, the two major serum porphyrin-binding proteins, show stoichiometries of 1 mol of porphyrin bound per mol of protein. The apparent dissociation constants, Kd, are in the range of 1-2 microM for albumin and 3-4 microM for haemopexin. These two major components of HpD would, after intravenous injection, bind to albumin and circulate in serum as albumin complexes. Free porphyrin rather than porphyrin bound to albumin interacts with Morris hepatoma tissue culture cells. A rapid high-affinity saturable transport system operates at free porphyrin concentrations of less than 2 microM. In addition, fluorescence spectra show that components in rat liver cytosol can bind haematoporphyrin and OO'-diacetylhaematoporphyrin and distinguish these binders from those present in rat serum.

Full text

PDF
503

Selected References

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

  1. Beaven G. H., Chen S. H., d' Albis A., Gratzer W. B. A spectroscopic study of the haemin--human-serum-albumin system. Eur J Biochem. 1974 Feb 1;41(3):539–546. doi: 10.1111/j.1432-1033.1974.tb03295.x. [DOI] [PubMed] [Google Scholar]
  2. Berenbaum M. C., Bonnett R., Scourides P. A. In vivo biological activity of the components of haematoporphyrin derivative. Br J Cancer. 1982 Apr;45(4):571–581. doi: 10.1038/bjc.1982.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berns M. W., Dahlman A., Johnson F. M., Burns R., Sperling D., Guiltinan M., Siemens A., Walter R., Wright W., Hammer-Wilson M. In vitro cellular effects of hematoporphyrin derivative. Cancer Res. 1982 Jun;42(6):2325–2329. [PubMed] [Google Scholar]
  4. Chipman D. M., Grisaro V., Sharon N. The binding of oligosaccharides containing N-acetylglucosamine and N-acetylmuramic acid to lysozyme. The specificity of binding subsites. J Biol Chem. 1967 Oct 10;242(19):4388–4394. [PubMed] [Google Scholar]
  5. Conway T. P., Morgan W. T., Liem H. H., Muller-Eberhard U. Catabolism of photo-oxidized and desialylated hemopexin in the rabbit. J Biol Chem. 1975 Apr 25;250(8):3067–3073. [PubMed] [Google Scholar]
  6. Cortese D. A., Kinsey J. H., Woolner L. B., Payne W. S., Sanderson D. R., Fontana R. S. Clinical application of a new endoscopic technique for detection of in situ bronchial carcinoma. Mayo Clin Proc. 1979 Oct;54(10):635–641. [PubMed] [Google Scholar]
  7. Dagher F. J., Lyons J. H., Finlayson D. C., Shamsai J., Moore F. D. Blood volume measurement: a critical study prediction of normal values: controlled measurement of sequential changes: choice of a bedside method. Adv Surg. 1965;1:69–109. [PubMed] [Google Scholar]
  8. Davies D. M., Smith A., Muller-Eberhard U., Morgan W. T. Hepatic subcellular metabolism of heme from heme-hemopexin: incorporation of iron into ferritin. Biochem Biophys Res Commun. 1979 Dec 28;91(4):1504–1511. doi: 10.1016/0006-291x(79)91235-x. [DOI] [PubMed] [Google Scholar]
  9. Dougherty T. J., Grindey G. B., Fiel R., Weishaupt K. R., Boyle D. G. Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light. J Natl Cancer Inst. 1975 Jul;55(1):115–121. doi: 10.1093/jnci/55.1.115. [DOI] [PubMed] [Google Scholar]
  10. Dougherty T. J., Kaufman J. E., Goldfarb A., Weishaupt K. R., Boyle D., Mittleman A. Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 1978 Aug;38(8):2628–2635. [PubMed] [Google Scholar]
  11. Gregorie H. B., Jr, Horger E. O., Ward J. L., Green J. F., Richards T., Robertson H. C., Jr, Stevenson T. B. Hematoporphyrin-derivative fluorescence in malignant neoplasms. Ann Surg. 1968 Jun;167(6):820–828. doi: 10.1097/00000658-196806000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henderson R. W., Christie G. S., Clezy P. S., Lineham J. Haematoporphyrin diacetate: a probe to distinguish malignant from normal tissue by selective fluorescence. Br J Exp Pathol. 1980 Aug;61(4):345–350. [PMC free article] [PubMed] [Google Scholar]
  13. Kessel D. Transport and binding of hematoporphyrin derivative and related porphyrins by murine leukemia L1210 cells. Cancer Res. 1981 Apr;41(4):1318–1323. [PubMed] [Google Scholar]
  14. Koskelo P., Toivonen I., Rintola P. The binding of 14C-labelled porphyrins by plasma proteins. Clin Chim Acta. 1970 Sep;29(3):559–565. doi: 10.1016/0009-8981(70)90028-8. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  16. Lamola A. A., Asher I., Muller-Eberhard U., Poh-Fitzpatrick M. Fluorimetric study of the binding of protoporphyrin to haemopexin and albumin. Biochem J. 1981 Jun 15;196(3):693–698. doi: 10.1042/bj1960693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mapes J. P., Aultman K. S. Effectors of fatty acid synthesis in hepatoma tissue culture cells. Arch Biochem Biophys. 1982 Apr 1;214(2):782–791. doi: 10.1016/0003-9861(82)90085-6. [DOI] [PubMed] [Google Scholar]
  18. Moan J., Christensen T. Photodynamic effects on human cells exposed to light in the presence of hematoporphyrin. Localization of the active dye. Cancer Lett. 1981 Jan;11(3):209–214. doi: 10.1016/0304-3835(81)90109-9. [DOI] [PubMed] [Google Scholar]
  19. Morgan W. T. Porphyrin-binding proteins in serum. Ann N Y Acad Sci. 1975 Apr 15;244:624–650. doi: 10.1111/j.1749-6632.1975.tb41558.x. [DOI] [PubMed] [Google Scholar]
  20. Morgan W. T., Smith A., Koskelo P. The interaction of human serum albumin and hemopexin with porphyrins. Biochim Biophys Acta. 1980 Jul 24;624(1):271–285. doi: 10.1016/0005-2795(80)90246-9. [DOI] [PubMed] [Google Scholar]
  21. Reddi E., Ricchelli F., Jori G. Interaction of human serum albumin with hematoporphyrin and its Zn(2)+-and Fe(3)+-derivatives. Int J Pept Protein Res. 1981 Oct;18(4):402–408. doi: 10.1111/j.1399-3011.1981.tb02998.x. [DOI] [PubMed] [Google Scholar]
  22. Sandberg S. Protoporphyrin-induced photodamage to mitochondria and lysosomes from rat liver. Clin Chim Acta. 1981 Mar 19;111(1):55–60. doi: 10.1016/0009-8981(81)90420-4. [DOI] [PubMed] [Google Scholar]
  23. Sandberg S., Romslo I. Porphyrin-induced photodamage at the cellular and the subcellular level as related to the solubility of the porphyrin. Clin Chim Acta. 1981 Jan 22;109(2):193–201. doi: 10.1016/0009-8981(81)90334-x. [DOI] [PubMed] [Google Scholar]
  24. Smith A., Morgan W. T. Haem transport to the liver by haemopexin. Receptor-mediated uptake with recycling of the protein. Biochem J. 1979 Jul 15;182(1):47–54. doi: 10.1042/bj1820047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tipping E., Ketterer B., Koskelo P. The binding of porphyrins by ligandin. Biochem J. 1978 Mar 1;169(3):509–516. doi: 10.1042/bj1690509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vretblad P., Hjorth R. The use of wheat-germ lectin-Sepharose for the purification of human haemopexin. Biochem J. 1977 Dec 1;167(3):759–764. doi: 10.1042/bj1670759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weishaupt K. R., Gomer C. J., Dougherty T. J. Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res. 1976 Jul;36(7 Pt 1):2326–2329. [PubMed] [Google Scholar]
  28. Zalar G. L., Poh-Fitzpatrick M., Krohn D. L., Jacobs R., Harber L. C. Induction of drug photosensitization in man after parenteral exposure to hematoporphyrin. Arch Dermatol. 1977 Oct;113(10):1392–1397. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES