Lipidomic and transcriptional analysis of the linoleoyl-omega-hydroxyceramide biosynthetic pathway in human psoriatic lesions

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Changes in levels of omega‐O‐acylceramides and related processing enzymes of sun‐exposed and sun‐protected facial stratum corneum in differently pigmented ethnic groups

“…The elevated omega‐O‐acylceramides observed in the Albino African women may indicate one of the reasons for additional corneocyte lipid scaffold and corneocyte maturation abnormality we observed in the Albino Africans previously, namely elevated levels of immature corneocytes [8]. Omega‐O‐acylceramides, especially the linoleate‐containing ones, are used in a complex enzymatic process to attach ceramides to the corneocyte protein envelope (CPE) [13–18]. Reduced levels of 12R‐LOX and eLOX3 were reported in photodamaged cheek SC previously from Caucasian women and 12R‐LOX in Chinese subjects [38–40].…”

“…Not only can these differences possibly contribute to the presence of immature and fragile CEs on the photodamaged SC site from all three ethnicities that we reported previously [8], but the excessive amounts of fragile CEs in the Albino Africans are not solely related to these particular enzyme levels. SDR9C7 is also purported to be involved in the linoleoyl-omega-O-acylceramide transformation process, and its mass levels were equally reduced in the Albino African subjects compared with the other two ethnicities (Table 1C) [13][14][15][16][17][18]. A reduction of at least these three enzymes involved in the process of corneocyte lipid envelope (CLE) formation are probably contributing to the clear lipid scaffold disorder in the Albino African subjects.…”

“…Moreover, cheek samples in all ethnic groups had a greater prevalence of more immature corneocyte envelopes (CEf) as measured by reduced Nile red/involucrin staining compared with the PA site, possibly indicating lowered lipid hydrophobicity of the corneocyte protein envelope (CPE), due to alterations in linoleoyl-omega-O-acylceramide processing. However, Albino Africans had dramatically reduced levels of mature corneocyte envelopes on both test sites together with corneocyte parakeratosis [8,[13][14][15][16][17][18]. As a result, we were interested The 12 main intercellular ceramides observed in human SC are depicted in Figure 2 [10].…”

“…[12]. The enzymes responsible for linoleoyl-omega-hydroxy acylceramide processing are shown in Figure 3 [10, [13][14][15][16][17][18]. 12R-lipoxygenase (12R-LOX) oxygenates the linoleic acid attached to the omega-O-acylceramide species (CER EOX) [14,15], epidermal lipoxygenase-3 (e-LOX3) then isomerizes the resulting hydroperoxide [16], which is then dehydrogenated by short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) [17] or converted to a linoleoyl triol by (EPHX3) [18] and cleaved by an unknown esterase.…”

“…12R-lipoxygenase (12R-LOX) oxygenates the linoleic acid attached to the omega-O-acylceramide species (CER EOX) [14,15], epidermal lipoxygenase-3 (e-LOX3) then isomerizes the resulting hydroperoxide [16], which is then dehydrogenated by short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) [17] or converted to a linoleoyl triol by (EPHX3) [18] and cleaved by an unknown esterase. The latter two products are then attached to the corneocyte envelope by transglutaminase 1 (TG1) [13,17]. The SDR9C7 product may also attach to the corneocyte protein envelope (CPE) through a reversible covalent binding [17].…”