Effects of porphyrins on proteins of cytosol and plasma. In vitro photo-oxidation and cross-linking of proteins by naturally occurring and synthetic porphyrins.
We examined the photodynamic effects of porphyrins, known photosensitizers, on proteins of cytosol and plasma that bind them and are implicated in their transport. Their susceptibility to photodecomposition by porphyrins was found to be higher than that of proteins with low or no affinity for tetrapyrroles. Inhibition of porphyrin binding by the addition of equimolar amounts of heme had no effect, indicating that protein photodecomposition may be induced, in part, by free or nonspecifically bound porphyrins. HBP, a heme-binding Z protein of liver cytosol, exhibited the highest susceptibility of all proteins tested, including glutathione S-transferases, albumin, hemopexin, and apotransferrin. HBP was extensively photo-oxidized, as evidenced by a decrease in its antigenicity and electrophoretic mobility, and it was cross-linked by naturally occurring porphyrins as well as by the synthetic tin-protoporphyrin and hematoporphyrin derivative. The water-soluble singlet oxygen scavengers L-histidine (50 mmol/L) and sodium azide (100 mmol/L) completely prevented the photodynamic effects of uroporphyrin (100 mumol/L) on HBP. Hydroxyl radical scavengers such as manitol and benzoate were partially effective, whereas water-insoluble singlet oxygen scavengers such as beta-carotene were totally ineffective. Preferential inhibition of cross-linking over other photodynamic effects of uroporphyrin was consistent with previous reports that cross-linking occurs subsequently to amino acid oxidation.
D000818:Animals; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D000939:Epitopes / Q000032:analysis; D005982:Glutathione Transferase / Q000378:metabolism; D006418:Heme / Q000494:pharmacology; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D006639:Histidine / Q000494:pharmacology; D046911:Macromolecular Substances; D010084:Oxidation-Reduction; D010777:Photochemistry; D011166:Porphyrins / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D001798:Blood Proteins; D002352:Carrier Proteins; D000939:Epitopes; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D046911:Macromolecular Substances; D011166:Porphyrins; D011506:Proteins; D006418:Heme; D006639:Histidine; D005982:Glutathione Transferase