Diminished protein-bound ω-hydroxylated ceramides in the skin of patients with ichthyosis with 12R-lipoxygenase (LOX) or eLOX-3 deficiency

Dick, Angela; Tantcheva-Poór, Illiana; Oji, Vinzenz; Giehl, Kathrin; Fischer, Judith; Krieg, Peter; Schneider, Holm; Rauh, Manfred

doi:10.1111/bjd.15406

Cited by 10 publications

(8 citation statements)

References 8 publications

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“…These observations help to clarify the function of 12R-LOX in the context of CLE formation and maturation. Similar to previous reports, 14,27 12R-LOX was found in the current study to be required for most CLE-CE cross-linking. However, this is the first report that CLE formation occurs independently of 12R-LOXedependent CLE-CE cross-linking.…”

Section: Discussionsupporting

confidence: 93%

Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking

Meyer

Crumrine

Schneider

et al. 2021

The American Journal of Pathology

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Section: Discussionsupporting

confidence: 93%

Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking

Meyer

Crumrine

Schneider

et al. 2021

The American Journal of Pathology

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“…As shown in Fig 1a, CLE plays an indispensable role in combining the corneocyte envelope with extracellular lamellar lipids. It has been reported that the amount of stratum corneum ceramides in patients with ichthyosis or atopic dermatitis is lower than in normal subjects [19, 21, 28]. This paucity of ceramides in these diseases is involved in the decrease of ceramide OS comprising the CLE [4].…”

Section: Discussionmentioning

confidence: 99%

Measurement of trihydroxy-linoleic acids in stratum corneum by tape-stripping: Possible biomarker of barrier function in atopic dermatitis

et al. 2019

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Epidermal ceramides are indispensable lipids that maintain the functions of the stratum corneum. Esterified omega-hydroxyacyl-sphingosine (EOS) ceramide with a linoleate moiety is one of the most important ceramide species for forming cornified lipid envelopes. This linoleate moiety is eventually metabolized to trihydroxy-linoleic acid (triol, 9,10,13-trihydroxy-11E-octadecenoic acid). Thus, we assumed that a decrease of triols might reflect skin barrier dysfunction. Against this background, the purposes of this study were to measure the triols by a simple tape-stripping method and to determine the correlation between the amount of triols and transepidermal water loss (TEWL) as an indicator of barrier dysfunction in atopic dermatitis patients. Twenty Japanese subjects with normal skin and 20 atopic dermatitis patients were enrolled in this study. TEWL was measured and triols of the stratum corneum were analyzed by tape-stripping. The results showed for the first time that triols in the stratum corneum could be simply measured using the tape-stripping method. The triol levels in atopic dermatitis patients were much higher than those in healthy subjects. Moreover, the triol levels correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis. The results suggest that the assaying of triol levels via non-invasive tape-stripping could be beneficial for monitoring barrier function in atopic dermatitis.

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“…We have clarified that SDR9C7 catalyzes the critical dehydrogenation of oxidized CerEOS to synthesize a highly reactive epoxy-enone derivative that is esterified in CerEOS [14]. The epoxy-enone is known to link nonenzymatically to proteins [14,80,81]. A plain a/bunsaturated ketone (enone) reacts with amino acid residues, cysteine, histidine, and lysine via Michael addition [82][83][84].…”

Section: Dehydrogenation and Binding Of Acylceramides To Ccementioning

confidence: 99%

Acylceramide is a key player in skin barrier function: insight into the molecular mechanisms of skin barrier formation and ichthyosis pathogenesis

Akiyama

2020

The FEBS Journal

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For a quarter of the century, tremendous advances have been achieved in our understanding of the pathogenic mechanisms and relevant genetic defects underlying ichthyoses and ichthyosis syndromes. Research on the pathogenic mechanisms of ichthyoses has provided novel insights into the synthesis and metabolism of epidermal ceramides. Conversely, our advanced understanding of the dynamics of ceramides in the epidermis has contributed to the clarification of the ichthyosis pathogenesis. Most ichthyosis subtypes have pathogenic processes related to stratum corneum barrier defects. Two essential structures of the stratum corneum barrier, the corneocyte lipid envelope (CLE) and the intercellular lipid layers, consist of epidermal functional lipids. Ceramides are included in the most significant components of the functional lipid in the epidermis. Acylceramides, particularly EOS, which is a combination of esterified x-hydroxy ultra-long-chain fatty acids and sphingosines, are critical as the main component of the CLE. Molecules encoded by a number of ichthyosis-causative genes (ABCA12, ALOXE3, ALOX12B, CYP4F22, CERS3, ABHD5, PNPLA1, ELOVL4, and SDR9C7) are known to be involved in the synthesis, transport, and metabolism of acylceramide, and in the formation of the CLE. This review focuses on the processes of acylceramide biosynthesis and the steps of CLE formation in the stratum corneum. I sum up the pathogenic mechanisms of autosomal recessive congenital ichthyosis and various ichthyosis syndromes from the viewpoints of the defective synthesis, metabolism, and transport of acylceramide and the failure of CLE formation.

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Diminished protein-bound ω-hydroxylated ceramides in the skin of patients with ichthyosis with 12R-lipoxygenase (LOX) or eLOX-3 deficiency

Cited by 10 publications

References 8 publications

Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking

Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking

Measurement of trihydroxy-linoleic acids in stratum corneum by tape-stripping: Possible biomarker of barrier function in atopic dermatitis

Acylceramide is a key player in skin barrier function: insight into the molecular mechanisms of skin barrier formation and ichthyosis pathogenesis

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