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

Meyer, Jason M.; Crumrine, Debra; Schneider, Holm; Dick, Angela; Schmuth, Matthias; Gruber, Robert; Radner, Franz P.W.; Grond, Susanne; Wakefield, Joan S.; Mauro, Theodora M.; Elias, Peter M.

doi:10.1016/j.ajpath.2021.02.005

Cited by 9 publications

(5 citation statements)

References 29 publications

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“…Their plasma membranes are replaced by cornified envelopes (CEs), insoluble and chemically resistant structures made from transglutaminase (TGM)-mediated cross-linked protein (Evora et al 2021). With their attached lipids, CEs constitute a specialized hydrophobic barrier to the environment (Meyer et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes

Lin,

Durbin-Johnson,

Rocke

et al. 2023

Toxicological Sciences

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Cornified envelopes (CEs) of human epidermis ordinarily consist of transglutaminase-mediated cross-linked proteins and are essential for skin barrier function. However, in addition to enzyme-mediated isopeptide bonding, protein cross-linking could also arise from oxidative damage. Our group recently demonstrated abnormal incorporation of cellular proteins into CEs by pro-oxidants in woodsmoke. In this study, we focused on 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to further understand the mechanisms through which environmental pro-oxidants induce CE formation and alter the CE proteome. CEs induced by the ionophore X537A were used for comparison. Similar to X537A, DMNQ- and MLS-induced CE formation was associated with membrane permeabilization. However, since DMNQ is non-adduct forming, its CEs were similar in protein profile to those from X537A. By contrast, MLS, rich in reactive carbonyls that can form protein adducts, caused a dramatic change in the CE proteome. TCDD-CEs were found to contain many CE precursors, such as small proline-rich proteins and late cornified envelope proteins, encoded by the epidermal differentiation complex. Since expression of these proteins is mediated by the aryl hydrocarbon receptor (AhR), and its well-known target protein, CYP1A1, was exclusively present in the TCDD group, we suggest that TCDD alters the CE proteome through persistent AhR activation. This study demonstrates the potential of environmental pro-oxidants to alter the epidermal CE proteome and indicates that the cellular redox state has an important role in CE formation.

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Section: Introductionmentioning

confidence: 99%

Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes

Lin,

Durbin-Johnson,

Rocke

et al. 2023

Toxicological Sciences

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“…This assumption is consistent with the ultrastructural data on CLE maturation in mice from ≈2.3 nm thick immature CLE in the initial SC layers to a 4.4 nm thick mature CLE in healthy mice. [ 37 ] The ability of tethered lipids to attract selected lipids, reorganize lipid domains in giant unilamellar vesicles, and, in some cases, completely sequester lipid phases on the interacting surface [ 38 ] appears to be highly relevant to the abovementioned CLE behavior. Cytochemical reaction with filipin indicates that CLEs are devoid of cholesterol.…”

Section: Resultsmentioning

confidence: 99%

Lipid Monolayer on Cell Surface Protein Templates Functional Extracellular Lipid Assembly

Dwivedi,

Mazumder,

Pullmannová

et al. 2024

Small

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When the ancestors of men moved from aquatic habitats to the drylands, their evolutionary strategy to restrict water loss is to seal the skin surface with lipids. It is unknown how these rigid ceramide‐dominated lipids with densely packed chains squeeze through narrow extracellular spaces and how they assemble into their complex multilamellar architecture. Here it is shown that the human corneocyte lipid envelope, a monolayer of ultralong covalently bound lipids on the cell surface protein, templates the functional barrier assembly by partly fluidizing and rearranging the free extracellular lipids in its vicinity during the sculpting of a functional skin lipid barrier. The lipid envelope also maintains the fluidity of the extracellular lipids during mechanical stress. This local lipid fluidization does not compromise the permeability barrier. The results provide new testable hypotheses about epidermal homeostasis and the pathophysiology underlying diseases with impaired lipid binding to corneocytes, such as congenital ichthyosis. In a broader sense, this lipoprotein‐mediated fluidization of rigid (sphingo)lipid patches may also be relevant to lipid rafts and cellular signaling events and inspire new functional materials.

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“…Skin samples were minced into fragments < 0.5 mm 3 , prefixed in half-strength Karnovsky’s fixative, rinsed three times in 0.1 mol/L cacodylate buffer, followed by postfixation in ruthenium tetroxide (Polysciences). Samples were then embedded in epoxy-Epon (Hexion) and processed for electron microscopy ( 36 ). Imaging was done on thin sections using a JEOL 100CX electron microscope at 60 V with a Gatan Bioscan camera (model 792).…”

Section: Methodsmentioning

confidence: 99%

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

Opálka

Meyer

Ondrejčeková

et al. 2022

Journal of Lipid Research

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

Cited by 9 publications

References 29 publications

Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes

Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes

Lipid Monolayer on Cell Surface Protein Templates Functional Extracellular Lipid Assembly

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

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