title: Potentiation of hyperthermia-induced haemolysis of human erythrocytes by photodynamic treatment. Evidence for the involvement of the anion transporter in this synergistic interaction.
abstract: Heat treatment of human erythrocytes led to increased passive cation permeability, followed by haemolysis. K+ leakage was linear up to a loss of about 80% in the temperature range 46-54 degrees C. Kinetic analysis of the results revealed an activation energy of 246 kJ/mol, implicating a transition in the membrane as critical step. Pretreatment of erythrocytes with 4,4'-di-isothiocyano-2,2'-stilbenedisulphonate, chymotrypsin or chlorpromazine caused a potentiation of subsequent heat-induced K+ leakage. Photodynamic treatment of erythrocytes with Photofrin II, eosin isothiocyanate or a porphyrin-Cu2+ complex as sensitizer also induced an increase in passive cation permeability, ultimately resulting in colloid osmotic haemolysis. The combination of photodynamic treatment immediately followed by hyperthermia had a synergistic effect on K+ leakage. Analysis of the results by the Arrhenius equation revealed that both the activation energy and the frequency factor of heat-induced K+ leakage were decreased significantly by preceding photodynamic treatment, suggesting that hyperthermia and photodynamic treatment have a common target for the induction of K+ leakage. Several lines of reasoning indicate that this common target is band 3. A model is thus proposed for the observed potentiation of hyperthermically induced K+ leakage by photodynamic treatment, in which photo-oxidation of band 3 results in increased sensitivity to subsequent thermal denaturation. These phenomena may be of more general significance, as photodynamic treatment and hyperthermia interacted synergistically with respect to K+ leakage with L929 fibroblasts also.
authors.affiliation: Sylvius Laboratories, Department of Medical Biochemistry, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Prinsze
authors.forename: K
authors.initials: K
authors.lastname: Tijssen
authors.forename: T M
authors.initials: TM
authors.lastname: Dubbelman
authors.forename: J
authors.initials: J
authors.lastname: Van Steveninck
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000097:blood*; D017323:Dihematoporphyrin Ether; D004307:Dose-Response Relationship, Radiation; D004801:Eosine Yellowish-(YS) / Q000494:pharmacology / Q000031:analogs & derivatives; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006415:Hematoporphyrins / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D007739:L Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D051379:Mice; D011188:Potassium / Q000097:blood / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; C012957:eosine-5-isothiocyanate; D017323:Dihematoporphyrin Ether; D011188:Potassium; D004801:Eosine Yellowish-(YS)