Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models
Ceramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C &...
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2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7468 |
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| author | Andrej Kováčik Petra Pullmannová Lukáš Opálka Michaela Šilarová Jaroslav Maixner Kateřina Vávrová |
| author_facet | Andrej Kováčik Petra Pullmannová Lukáš Opálka Michaela Šilarová Jaroslav Maixner Kateřina Vávrová |
| author_sort | Andrej Kováčik |
| collection | DOAJ |
| description | Ceramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C <sub>16</sub>-C <sub>24</sub>)/cholesterol, and a minor component, cholesteryl sulfate. Namely, Cers with (<i>R</i>)-α-hydroxy lignoceroyl chains attached to sphingosine (Cer AS), dihydrosphingosine (Cer AdS), and phytosphingosine (Cer AP) were compared to their unnatural (<i>S</i>)-diastereomers and to Cers with non-hydroxylated lignoceroyl chains attached to sphingosine (Cer NS), dihydrosphingosine (Cer NdS), and phytosphingosine (Cer NP). By comparing several biophysical parameters (lamellar organization by X-ray diffraction, chain order, lateral packing, phase transitions, and lipid mixing by infrared spectroscopy using deuterated lipids) and the permeabilities of these models (water loss and two permeability markers), we conclude that there is no general or common consequence of Cer α-hydroxylation. Instead, we found a rich mix of effects, highly dependent on the sphingoid base chain, configuration at the α-carbon, and permeability marker used. We found that the model membranes with unnatural Cer (<i>S</i>)-AS have fewer orthorhombically packed lipid chains than those based on the (<i>R</i>)-diastereomer. In addition, physiological (<i>R</i>)-configuration decreases the permeability of membranes, with Cer (<i>R</i>)-AdS to theophylline, and increases the lipid chain order in model systems with natural Cer (<i>R</i>)-AP. Thus, each Cer subclass makes a distinct contribution to the structural organization and function of the skin lipid barrier. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:37:29Z |
| publishDate | 2021-07-01 |
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| spelling | doaj.art-a19bbe08947642c8af95f01768ffce092023-11-22T03:59:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214746810.3390/ijms22147468Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid ModelsAndrej Kováčik0Petra Pullmannová1Lukáš Opálka2Michaela Šilarová3Jaroslav Maixner4Kateřina Vávrová5Skin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicSkin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicSkin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicSkin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicFaculty of Chemical Technology, University of Chemistry and Technology in Prague, Technická 5, 166 28 Prague, Czech RepublicSkin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicCeramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C <sub>16</sub>-C <sub>24</sub>)/cholesterol, and a minor component, cholesteryl sulfate. Namely, Cers with (<i>R</i>)-α-hydroxy lignoceroyl chains attached to sphingosine (Cer AS), dihydrosphingosine (Cer AdS), and phytosphingosine (Cer AP) were compared to their unnatural (<i>S</i>)-diastereomers and to Cers with non-hydroxylated lignoceroyl chains attached to sphingosine (Cer NS), dihydrosphingosine (Cer NdS), and phytosphingosine (Cer NP). By comparing several biophysical parameters (lamellar organization by X-ray diffraction, chain order, lateral packing, phase transitions, and lipid mixing by infrared spectroscopy using deuterated lipids) and the permeabilities of these models (water loss and two permeability markers), we conclude that there is no general or common consequence of Cer α-hydroxylation. Instead, we found a rich mix of effects, highly dependent on the sphingoid base chain, configuration at the α-carbon, and permeability marker used. We found that the model membranes with unnatural Cer (<i>S</i>)-AS have fewer orthorhombically packed lipid chains than those based on the (<i>R</i>)-diastereomer. In addition, physiological (<i>R</i>)-configuration decreases the permeability of membranes, with Cer (<i>R</i>)-AdS to theophylline, and increases the lipid chain order in model systems with natural Cer (<i>R</i>)-AP. Thus, each Cer subclass makes a distinct contribution to the structural organization and function of the skin lipid barrier.https://www.mdpi.com/1422-0067/22/14/7468skin barrierstratum corneumlipidsceramideshydroxylationbiophysics |
| spellingShingle | Andrej Kováčik Petra Pullmannová Lukáš Opálka Michaela Šilarová Jaroslav Maixner Kateřina Vávrová Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models International Journal of Molecular Sciences skin barrier stratum corneum lipids ceramides hydroxylation biophysics |
| title | Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models |
| title_full | Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models |
| title_fullStr | Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models |
| title_full_unstemmed | Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models |
| title_short | Effects of (<i>R</i>)- and (<i>S</i>)-α-Hydroxylation of Acyl Chains in Sphingosine, Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models |
| title_sort | effects of i r i and i s i α hydroxylation of acyl chains in sphingosine dihydrosphingosine and phytosphingosine ceramides on phase behavior and permeability of skin lipid models |
| topic | skin barrier stratum corneum lipids ceramides hydroxylation biophysics |
| url | https://www.mdpi.com/1422-0067/22/14/7468 |
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