Effects of Ceramide and Dihydroceramide Stereochemistry at C-3 on the Phase Behavior and Permeability of Skin Lipid Membranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382594" target="_blank" >RIV/00216208:11160/18:10382594 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.acs.org/doi/10.1021/acs.langmuir.7b03448" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.langmuir.7b03448</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.langmuir.7b03448" target="_blank" >10.1021/acs.langmuir.7b03448</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effects of Ceramide and Dihydroceramide Stereochemistry at C-3 on the Phase Behavior and Permeability of Skin Lipid Membranes

Popis výsledku v původním jazyce

Ceramides (Cer) are key components of the skin permeability barrier. Sphingosine-based CerNS and dihydrosphingosine-based CerNdS (dihydroCer) have two chiral centers; however, the importance of the correct stereochemistry in the skin barrier Cer is unknown. We investigated the role of the configuration at C-3 of CerNS and CerNdS in the organization and permeability of model skin lipid membranes. Unnatural L-threo-CerNS and L-threo-CerNdS with 24-C acyl chains were synthesized and, along with their natural D-erythro-isomers, incorporated into membranes composed of major stratum corneum lipids (Cer, free fatty acids, cholesterol, and cholesteryl sulfate). The membrane microstructure was investigated by X-ray powder diffraction and infrared spectroscopy, including deuterated free fatty acids. Inversion of the C-3 configuration in CerNS and CerNdS increased phase transition temperatures, had no significant effects on lamellar phases, but also decreased the proportion of orthorhombic packing and decreased lipid mixing in the model membranes. These changes in membrane organization resulted in membrane permeabilities that ranged from unchanged to 5-fold higher (depending on the permeability markers, namely, water loss, electrical impedance, flux of theophylline, and flux of indomethacin) compared to membranes with natural CerNS/NdS isomers. Thus, the physiological D-erythro stereochemistry of skin Cer and dihydroCer appears to be essential for their correct barrier function.

Název v anglickém jazyce

Effects of Ceramide and Dihydroceramide Stereochemistry at C-3 on the Phase Behavior and Permeability of Skin Lipid Membranes

Popis výsledku anglicky

Ceramides (Cer) are key components of the skin permeability barrier. Sphingosine-based CerNS and dihydrosphingosine-based CerNdS (dihydroCer) have two chiral centers; however, the importance of the correct stereochemistry in the skin barrier Cer is unknown. We investigated the role of the configuration at C-3 of CerNS and CerNdS in the organization and permeability of model skin lipid membranes. Unnatural L-threo-CerNS and L-threo-CerNdS with 24-C acyl chains were synthesized and, along with their natural D-erythro-isomers, incorporated into membranes composed of major stratum corneum lipids (Cer, free fatty acids, cholesterol, and cholesteryl sulfate). The membrane microstructure was investigated by X-ray powder diffraction and infrared spectroscopy, including deuterated free fatty acids. Inversion of the C-3 configuration in CerNS and CerNdS increased phase transition temperatures, had no significant effects on lamellar phases, but also decreased the proportion of orthorhombic packing and decreased lipid mixing in the model membranes. These changes in membrane organization resulted in membrane permeabilities that ranged from unchanged to 5-fold higher (depending on the permeability markers, namely, water loss, electrical impedance, flux of theophylline, and flux of indomethacin) compared to membranes with natural CerNS/NdS isomers. Thus, the physiological D-erythro stereochemistry of skin Cer and dihydroCer appears to be essential for their correct barrier function.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GC16-25687J" target="_blank" >GC16-25687J: Vztahy mezi zánětlivými procesy a bariérovými lipidy u onemocnění kůže</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Langmuir

ISSN

0743-7463

e-ISSN

—

Svazek periodika

34

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

521-529

Kód UT WoS článku

000422611500062

EID výsledku v databázi Scopus

2-s2.0-85039051533