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PHOTOSENSITIZING EFFECTS OF HEMATOPORPHYRIN DERIVATIVE IMMOBILIZED ON SEPHAROSE
Author(s) -
Gibson Scott L.,
Murant Richard S.,
Hilf Russell
Publication year - 1987
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1987.tb08409.x
Subject(s) - hematoporphyrin , chemistry , membrane , sepharose , biochemistry , succinylation , organelle , mitochondrion , malate dehydrogenase , biophysics , inner mitochondrial membrane , enzyme , photodynamic therapy , organic chemistry , biology , acetylation , gene
— The cytotoxicity that ensues following photosensitization by hematoporphyrin derivative (Hpd) is attributed to production of singlet oxygen. Many of the cellular end points reported to be affected are localized to membranes, hydrophobic environments conducive to partitioning of hydrophobic porphyrins in Hpd. In order to test the hypothesis that efficacy of Hpd‐induced photosensitization is enhanced by its ability to freely enter cells or subcellular organelles, we immobilized Hpd on a sepharose support. This immobilized reagent was found to produce 1 O 2 when photoradiated, in yields similar to those observed for Hpd in solution, as evidenced by the bleaching of p ‐nitrosodimethylaniline in the presence of imidazole. The immobilized Hpd was capable of photosensitizing, i.e. inhibit, cytochrome c oxidase activity in intact mitochondrial membranes and in aqueous solution. However, enzymes located on the interior of mitochondrial membranes (F 0 F 1 ATP synthase and succinate dehydrogenase), in the mitochondrial matrix (malate dehydrogenase), or on the inside of the plasma membrane, (Na++ K+)‐ ATPase, were unaffected by immobilized Hpd plus photoradiation compared to free Hpd. The results suggest that photosensitization by Hpd most likely arises from entry of the photosensitizer into the biological membrane, although proteins on the exterior membrane surface may be susceptible to damage by 1 O 2 produced in proximity to their location.