Transmembrane localization of cis-isomers of zeaxanthin in the host dimyristoylphosphatidylcholine bilayer membrane

Abstract

The effects of the 9-cis and 13-cis isomers of zeaxanthin on the molecular organization and dynamics of dimyristoylphosphatidylcholine (DMPC) membranes were investigated using conventional and saturation recovery EPR observations of the 1-palmitoyl-2-(14-doxylstearoyl)phosphatidylcholine (14-PC) spin label. The results were compared with the effects caused by the all-trans isomer of zeaxanthin. Effects on membrane fluidity, order, hydrophobicity, and the oxygen transport parameter were monitored at the center of the fluid phase DMPC membrane. The local diffusion-solubility product of oxygen molecules (oxygen transport parameter) in the membrane center, studied by saturation-recovery EPR, decreased by 47% and 27% by including 10 mol% 13-cis and 9-cis zeaxanthin, respectively; whereas, incorporation of all-trans zeaxanthin decreased this parameter by only 11%. At a zeaxanthin-to-DMPC mole ratio of 1:9, all investigated isomers decreased the membrane fluidity and increased the alkyl chain order in the membrane center. They also increased the hydrophobicity of the membrane interior. The effects of these isomers of zeaxanthin on the membrane properties mentioned above increase as: all-trans<9-cis<or=13-cis. Obtained results suggest that the investigated cis-isomers of zeaxanthin, similar to the all-trans isomer, are located in the membrane interior, adopting transmembrane orientation with the polar terminal hydroxyl groups located in the opposite leaflets of the bilayer. However, the existence of the second pool of cis-zeaxanthin molecules located in the one leaflet and anchored by the terminal hydroxyl groups in the same polar headgroup region cannot be completely ruled out.

Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein

“…However, distinct intramembrane localization of the stereoisomers may explain their different behavior. In agreement with this idea, Widomska and Subczynski have demonstrated that cis and trans isomers of zeaxanthin have different orientations in dimyristoyl phosphatidylcholine bilayer membranes and thus can modify the biophysical membrane properties, including the hydrophobicity and membrane fluidity at different depth of the membrane 40 . In accordance with this report our fluorescence anisotropy measurements revealed that the retinoid derivatives interacting with the transporters retinyl-acetate, 13- cis -retinoic acid and retinol selectively increase the membrane viscosity and packing density in the depth of the membrane monitored by DPH, while ATRA and 9- cis -retinoic acid did not have any effect ( Fig.…”

Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes

“…Monopolar β-cryptoxanthin is also less soluble in the lipid bilayer than macular xanthophylls [41]. Interestingly, the tendency of cis -isomers of xanthophylls to aggregate is usually much less than their all- trans counterparts [42,43], and they also affect membrane properties more strongly (the effect of zeaxanthin on membrane properties increases in the direction: all- trans < 9- cis ≤ 13- cis [44]). Cis -isomers are also more readily solubilized, absorbed, and transported [42].…”

“…Orientation of polar and nonpolar carotenoids (including their cis -forms) in the lipid-bilayer membrane has been investigated by many laboratories [19,44,47,58,59]. It is suggested that the presence of polar hydroxyl groups at the ends of carotenoid molecules and their transmembrane orientation (as in the case of zeaxanthin and lutein) enhance their antioxidant properties , as compared with the antioxidant properties of monopolar (β-cryptoxanthin) and nonpolar (β-carotene) carotenoids [40,60].…”

Calorimetric studies of the effect of cis-carotenoids on the thermotropic phase behavior of phosphatidylcholine bilayers

“…magnetic resonance (NMR) [21] spectroscopy, diffractometry [22,23], monolayers technique [24], and others. However, the effect of the cis-isomers of carotenoids on the membrane properties is less investigated [25,26].…”