omega-O-Acylceramides but not omega-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

omega-O-Acylceramides but not omega-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

omega-O-Acylceramides but not omega-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of Lipid Research

ISSN

0022-2275

e-ISSN

1539-7262

Svazek periodika

63

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

100226

Kód UT WoS článku

000833522400003

EID výsledku v databázi Scopus

2-s2.0-85131877849