Biomedical subjects

Paul D Sima

Publications and source records attributed to Paul D Sima.

3 recordsLinked to original sources

PubMed2005

Synthetic carotenoid derivatives prevent photosensitised killing of retinal pigment epithelial cells more effectively than lutein.

We studied the photosensitised killing of retinal pigment epithelial (RPE) cells using two photosensitisers that localise in lysosomes. The ARPE-19 cell line was photosensitised using either acridine orange or cis-di(4-sulfonatophenyl)diphenylporphine. We then measured the amount of photoprotection provided to RPE cells by five synthetic carotenoid derivatives and by lutein. The synthetic carotenoid derivatives studied were the Girard's reagent P derivative (GRP) of retinal (GRP-retinal), the GRP derivative of beta-apo-8'-carotenal (GRP-carotenal), the Girard's reagent T derivative of beta-apo-8'-carotenal (GRT-carotenal), the GRP derivative of canthaxanthin ((GRP)2-canthaxanthin) and the dansyl hydrazine derivative of beta-apo-8'-carotenal (dansyl-carotenal). We found that GRP-carotenal, GRT-carotenal (GRP)2-canthaxanthin and dansyl-carotenal were effective photoprotectors. All of these carotenoids had large singlet-oxygen quenching constants and had chemical structures designed to localise either in mitochondria or in lysosomes. In contrast, lutein and GRP-retinal were not effective photoprotectors. The failure of GRP-retinal to provide significant photoprotection may have been due to its relatively low singlet-oxygen quenching constant. Lutein is a potent singlet-oxygen quencher, but may not have provided significant photoprotection in this model because the lutein may have had a different subcellular distribution than the photosensitisers used.

Antioxidants↗

PubMed2003

Singlet-oxygen generation from A2E.

Singlet-oxygen generation was measured in solutions containing equilibrium mixtures of the retinal lipofuscins, 2-[2, 6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)- 1E,3E,5E,7Eoctatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) and double bond isomer of A2E (iso-A2E), using steady-state irradiation and using cholesterol as a singlet-oxygen trap. The amount of singlet oxygen generated by equilibrium mixtures of A2E and iso-A2E was compared with that generated by tetraphenylporphine (TPP) under the same conditions. Studies were carried out in ethanol-d6, acetone-d6, 80% cyclohexane-d(12)-20% acetone-d6 (vol/vol) and hexafluorobenzene. Using 420 nm irradiation and assuming a singlet-oxygen quantum yield of 0.60 +/- 0.12 for TPP, the singlet-oxygen quantum yields were 0.8 +/- 0.3 x 10(-3), 1.2 +/- 0.4 x 10(-3), 2 +/- 1 x 10(-3) and 4 + 1 x 10(-3), respectively. In acetone-d6, the quantum yields were smaller at longer wavelengths, with values of 0.3 +/- 0.1 x 10(-3) and 0.4 +/- 0.2 x 10(-3) at 461 and 493 nm, respectively. Singlet-oxygen generation was greatest in solvents with the lowest dielectric constants. In view of the relatively small quantum yields, the contribution of singlet-oxygen generation to the phototoxic properties of A2E and of iso-A2E will require further study.

Aging↗

PubMedDate not supplied

Structural requirements for efficient cellular photoprotection by carotenoid derivatives.

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.

Acridine Orange↗