title: The influence of cupric ions on porphyrin-induced photodynamic membrane damage in human red blood cells.
abstract: Photooxidation of various susceptible substrates with hematoporphyrin derivative (photofrin) as sensitizer was strongly inhibited by simultaneous addition of cupric acetate to the reaction mixture. With sulfhydryl-containing compounds, however, an increased rate of photooxidation was observed under these experimental conditions. Preincubation of photofrin and cupric acetate at equimolar concentrations for 24 h at room temperature yielded a stable photofrin-Cu2+ complex. This complex did not act as photosensitizer with histidine, tryptophan, tyrosine, methionine or guanosine as substrates. With dithiothreitol, however, the photofrin-Cu2+ complex still acted as a photosensitizer, with an efficiency of about 30% as compared to free photofrin. Also in red blood cell membranes only sulfhydryl groups were photooxidized with the photofrin-Cu2+ complex as sensitizer. Illumination of intact erythrocytes in the presence of the photofrin-Cu2+ complex resulted in K+ leakage and, ultimately, photohemolysis. Pretreatment of the cells with N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited this photodynamically induced K+ loss. Considering recent studies on the reactivity of distinct membrane SH-groups with various sulfhydryl reagents this suggests that a sulfhydryl group, located in the 17 kDa membrane-bound fragment of band 3, is involved in photodynamic K+ leakage with the photofrin-Cu2+ complex as sensitizer.
authors.forename: J
authors.initials: J
authors.lastname: van Steveninck
authors.forename: J P
authors.initials: JP
authors.lastname: Boegheim
authors.forename: T M
authors.initials: TM
authors.lastname: Dubbelman
mesh_terms: D003300:Copper / Q000494:pharmacology*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005033:Ethylmaleimide / Q000494:pharmacology; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009942:Organometallic Compounds; D010777:Photochemistry; D011188:Potassium / Q000097:blood
chemical_list: D006415:Hematoporphyrins; D009942:Organometallic Compounds; C015092:cupric acetate; D017324:Hematoporphyrin Derivative; D003300:Copper; D004228:Dithionitrobenzoic Acid; D005033:Ethylmaleimide; D011188:Potassium