omega-O-Acylceramides but not omega-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F22%3A10450937" target="_blank" >RIV/00216208:11160/22:10450937 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EunNYumoYx" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EunNYumoYx</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jlr.2022.100226" target="_blank" >10.1016/j.jlr.2022.100226</a>
Alternative languages
Result language
angličtina
Original language name
omega-O-Acylceramides but not omega-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids
Original language description
Epidermal omega-O-acylceramides (omega-O-acylCers) are essential components of a competent skin barrier. These unusual sphingolipids with ultralong N-acyl chains contain linoleic acid esterified to the terminal hydroxyl of the N-acyl, the formation of which requires the transacylase activity of patatin-like phospholipase domain containing 1 (PNPLA1). In ichthyosis with dysfunctional PNPLA1, omega-O-acylCer levels are significantly decreased, and omega-hydroxylated Cers (omega-OHCers) accumulate. Here, we explore the role of the linoleate moiety in omega-O-acylCers in the assembly of the skin lipid barrier. Ultrastructural studies of skin samples from neonatal Pnpla1(+/+) and Pnpla1(-/-) mice showed that the linoleate moiety in omega-O-acylCers is essential for lamellar pairing in lamellar bodies, as well as for stratum corneum lipid assembly into the long periodicity lamellar phase. To further study the molecular details of omega-O-acylCer deficiency on skin barrier lipid assembly, we built in vitro lipid models composed of major stratum corneum lipid subclasses containing either omega-O-acylCer (healthy skin model), omega-OHCer (Pnpla1(-/-) model), or combination of the two. X-ray diffraction, infrared spectroscopy, and permeability studies indicated that omega-OHCers could not substitute for omega-O-acylCers, although in favorable conditions, they form a medium lamellar phase with a 10.8 nm-repeat distance and permeability barrier properties similar to long periodicity lamellar phase. In the absence of omega-O-acylCers, skin lipids were prone to separation into two phases with diminished barrier properties. The models combining omega-OHCers with omega-O-acylCers indicated that accumulation of omega-OHCers does not prevent omega-O-acylCer-driven lamellar stacking. These data suggest that omega-O-acylCer supplementation may be a viable therapeutic option in patients with PNPLA1 deficiency.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Lipid Research
ISSN
0022-2275
e-ISSN
1539-7262
Volume of the periodical
63
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
100226
UT code for WoS article
000833522400003
EID of the result in the Scopus database
2-s2.0-85131877849