Evidence That the Corneocyte Has a Chemically Bound Lipid Envelope

Swartzendruber, D. C.; Wertz, Philip W.; Madison, Kathi C.; Downing, Donald T.

doi:10.1111/1523-1747.ep12470383

Cited by 331 publications

(174 citation statements)

References 17 publications

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“…ester-linked) g-hydroxylated ceramides and fatty acids [2,3]. This lipid-bound envelope (LBE) is thought to be essential for the interaction of highly cross-linked proteins of the corneocyte (corni¢ed cell envelope, CE) with the extracellular lipid matrix [4]. It is well documented that the function of the stratum corneum as a barrier to excess transepidermal water loss highly depends on the presence of extracellular lipid membranes.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of protein‐bound epidermal glucosylceramides in β‐glucocerebrosidase deficient type 2 Gaucher mice

1999

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The epidermal permeability barrier for water is essentially maintained by extracellular lipid membranes within the interstices of the stratum corneum. Ceramides, the main components of these membranes, derive in large part from hydrolysis of glucosylceramides mediated by the lysosomal enzyme L L-glucocerebrosidase. As analyzed in this work, the L Lglucocerebrosidase deficiency in type 2 Gaucher mice (RecNci I) resulted in an accumulation of all epidermal glucosylceramide species accompanied with a decrease of the related ceramides. However, the levels of one ceramide subtype, which possesses an K K-hydroxypalmitic acid, was not altered in RecNci I mice suggesting that the L L-glucocerebrosidase pathway is not required for targeting of this lipid to interstices of the stratum corneum. Most importantly, g g-hydroxylated glucosylceramides which are protein-bound to the epidermal cornified cell envelope of the transgenic mice accumulated up to 35-fold whereas levels of related protein-bound ceramides and fatty acids were decreased to 10% of normal control. These data support the hypothesis that in wild-type epidermis g g-hydroxylated glucosylceramides are first transferred enzymatically from their linoleic esters to proteins of the epidermal cornified cell envelope and then catabolized to protein-bound ceramides and fatty acids, thus contributing at least in part to the formation of the lipid-bound envelope.z 1999 Federation of European Biochemical Societies.

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Section: Introductionmentioning

confidence: 99%

Accumulation of protein‐bound epidermal glucosylceramides in β‐glucocerebrosidase deficient type 2 Gaucher mice

1999

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“…1) (6 -9). These covalently bound lipids are the main component of the corneocyte lipid envelope (CLE) (10), which, together with the underlying CE, constitutes a structure indispensable to the integrity of the epidermal water barrier (5,11).…”

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confidence: 99%

Lipoxygenases Mediate the Effect of Essential Fatty Acid in Skin Barrier Formation

Zheng

Yin

Boeglin

et al. 2011

Journal of Biological Chemistry

138

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A barrier to water loss is vital to maintaining life on dry land. Formation of the mammalian skin barrier requires both the essential fatty acid linoleate and the two lipoxygenases 12R-lipoxygenase (12R-LOX) and epidermal lipoxygenase-3 (eLOX3), although their roles are poorly understood. Linoleate occurs in O-linoleoyl--hydroxyceramide, which, after hydrolysis of the linoleate moiety, is covalently attached to protein via the free -hydroxyl of the ceramide, forming the corneocyte lipid envelope, a scaffold between lipid and protein that helps seal the barrier. Here we show using HPLC-UV, LC-MS, GC-MS, and 1 H NMR that O-linoleoyl--hydroxyceramide is oxygenated in a regio-and stereospecific fashion by the consecutive actions of 12R-LOX and eLOX3 and that these products occur naturally in pig and mouse epidermis. 12R-LOX forms 9R-hydroperoxy-linoleoyl--hydroxyceramide, further converted by eLOX3 to specific epoxyalcohol (9R,10R-trans-epoxy-11E-13R-hydroxy) and 9-keto-10E,12Z esters of the ceramide; an epoxy-ketone derivative (9R,10R-trans-epoxy-11E-13-keto) is the most prominent oxidized ceramide in mouse skin. These products are absent in 12R-LOX-deficient mice, which crucially display a near total absence of protein-bound -hydroxyceramides and of the corneocyte lipid envelope and die shortly after birth from transepidermal water loss. We conclude that oxygenation of O-linoleoyl--hydroxyceramide is required to facilitate the ester hydrolysis and allow bonding of the -hydroxyceramide to protein, providing a coherent explanation for the roles of multiple components in epidermal barrier function. Our study uncovers a hitherto unknown biochemical pathway in which the enzymic oxygenation of ceramides is involved in building a crucial structure of the epidermal barrier.

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“…For example, it has been used to illustrate how penetration enhancers change the fluidity (disorganization) of lipid membranes. 105 Some models 106 take a closer look at the skin structure 107,108 and determine skin permeation as function of the stratum corneum permeation coefficient (KSC). The KSC is extrapolated to Kp using ''effective'' diffusivity and ''effective'' path lengths, which correspond to the diffusivity and thickness of an equivalent homogenous membrane having the same properties as the stratum corneum.…”

Section: In Silico Methodsmentioning

confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

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The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

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Evidence That the Corneocyte Has a Chemically Bound Lipid Envelope

Cited by 331 publications

References 17 publications

Accumulation of protein‐bound epidermal glucosylceramides in β‐glucocerebrosidase deficient type 2 Gaucher mice

Accumulation of protein‐bound epidermal glucosylceramides in β‐glucocerebrosidase deficient type 2 Gaucher mice

Lipoxygenases Mediate the Effect of Essential Fatty Acid in Skin Barrier Formation

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

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