Structural Requirements for Efficient Cellular Photoprotection by Carotenoid Derivatives¶†

Abstract

We have synthesized five carotenoid derivatives: (1) Girard's reagent P (GRP)-retinal from GRP and retinal; (2) GRP-carotenal from GRP and beta-apo-8'-carotenal; (3) Girard's reagent T (GRT)-carotenal from GRT and beta-apo-8'-carotenal; (4) (GRP2-canthaxanthin from 2 mol of GRP and 1 mol of canthaxanthin; and (5) dansyl hydrazine (DH)-carotenal from DH and beta-apo-8'-carotenal. The first three derivatives are cations, whereas the fourth is a dication and the fifth is a weak base. Using K562 cells, we compared the subcellular distribution of the synthetic carotenoid derivatives with two uncharged natural carotenoids, beta-carotene and beta-apo-8'-carotenal. The two natural carotenoids were present mainly within the cell membranes. The synthetic carotenoid derivatives were more broadly distributed among the cell organelles. The positively charged derivatives had relatively high concentrations in mitochondria, whereas DH-carotenal had a relatively high concentration in lysosomes. We also measured the amount of photoprotection provided by the synthetic and natural carotenoids for K562 cells labeled with a photosensitizer (hypericin, protoporphyrin IX or cis-di[4-sulfonatophenyl]diphenylporphine). In this model system, only carotenoid derivatives with a permanent positive charge provided significant photoprotection. Neither the two natural carotenoids nor DH-carotenal were effective photoprotectors.