Lipid Composition of Cohesive and Desquamated Corneocytes from Mouse Ear Skin

Ranasinghe, A. W.; Wertz, Philip W.; Downing, Donald T.; Mackenzie, Ian C.

doi:10.1111/1523-1747.ep12284246

Cited by 89 publications

(33 citation statements)

References 25 publications

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“…But CSO 4 levels in epidermis/SC are 1 order of magnitude higher than the levels in blood (140,142,144), likely explaining the prominence of skin versus other organ involvement in RXLI. Normally, CSO 4 constitutes ?5% of the total lipid of human SG, declining to ?1% of lipid mass in the outer SC, through ongoing hydrolysis of CSO 4 by SSase during SC transit (145,146) (Fig. 3).…”

Section: Rxlimentioning

confidence: 99%

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

Elias

Williams

Holleran

et al. 2008

Journal of Lipid Research

181

172

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Section: Rxlimentioning

confidence: 99%

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

Elias

Williams

Holleran

et al. 2008

Journal of Lipid Research

181

172

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“…Cholesterol sulfate formation occurs early on in human squamous development, suggesting a functional role at an early stage in differentiation (28). Cholesterol sulfate is rich in the upper layers of the human epidermis, where it gradually accumulates during keratinocyte differentiation, reaching levels that are 4-5% of total lipid content in the upper stratum granulosum (58,59), after which it undergoes sulfohydrolysis in the cornified layer and representation drops to 1% of total lipids (114,115). The cholesterol-cholesterol sulfate ratio in epithelial cells outside of the skin is normally about 500:1 (116), whereas in the normal stratum corneum the ratio is as low as 10:1 or 5:1 (117).…”

Section: Cholesterol Sulfate As a Regulatory Molecule In Skinmentioning

confidence: 99%

Cholesterol sulfate in human physiology: what's it all about?

Strott

Higashi

2003

Journal of Lipid Research

202

184

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Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles. -Strott, C. A., and Y. Higashi. Cholesterol sulfate in human physiology: what's it all about? J.

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“…CSO 4 is a ubiquitous cholesterol metabolite, the amount of which is determined by the relative activity of cholesterol sulfotransferase and cholesterol sulfatase enzymes (10). CSO 4 gradually accumulates during epidermal keratinocyte differentiation, peaking normally at levels of 4 -5% of total lipids in the upper stratum granulosum and it is hydrolyzed in the cornified layer, so that normal corneocyte scales contain less than 1% CSO 4 of total lipids (11,12). In XI the lack of its breakdown results in an elevated CSO 4 content in the basal and spinous layers, peaking at Ͼ10% (by weight) of total lipids in the stratum corneum (13).…”

mentioning

confidence: 99%

Cholesterol 3-Sulfate Interferes with Cornified Envelope Assembly by Diverting Transglutaminase 1 Activity from the Formation of Cross-links and Esters to the Hydrolysis of Glutamine

Nemes¹,

Demény²,

Marekov³

et al. 2000

Journal of Biological Chemistry

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The loss of transglutaminase 1 enzyme (TGase 1) activity causes lamellar ichthyosis. Recessive X-linked ichthyosis (XI) results from accumulation of excess cholesterol 3-sulfate (CSO 4 ) in the epidermis but the pathomechanism how elevated epidermal CSO 4 causes ichthyosis is largely unknown. Here we provide evidence that XI is also a consequence of TGase 1 dysfunction. TGase 1 is a key component of barrier formation in keratinocytes: it participates in the cross-linking of cell envelope (CE) structural proteins, and also forms the lipid bound envelope by esterification of long chain -hydroxyceramides onto CE proteins. Using involucrin and an epidermal -hydroxyceramide analog as substrates, kinetic analyses revealed that at membrane concentrations above 4 mol %, CSO 4 caused a marked and dose-dependent inhibitory effect on isopeptide and ester bond formation. Sequencing of tryptic peptides from TGase 1-reacted involucrin showed a large increase in deamidation of substrate glutamines. We hypothesize that supraphysiological levels of CSO 4 in keratinocyte membranes distort the structure of TGase 1 and facilitate the access of water into its active site causing hydrolysis of substrate glutamine residues. Our findings provide further evidence for the pivotal role of the TGase 1 enzyme in CE formation.Assembly of an effective epidermal barrier structure is an essential adaptation to terrestrial life. In mammals the outermost bulwark of this barrier is the cornified layer of the epidermis, composed of flattened corneocytes mortared together by orderly lipid laminae. During terminal differentiation, individual corneocytes acquire a specialized cell peripheral structure termed the cornified cell envelope (CE), 1 which is responsible for maintenance of mechanical and chemical protection and indirectly contributes to water permeability barrier (see Refs. 1 and 2, for reviews). The CE is composed of two parts. The ϳ10 nm thick protein envelope is formed by covalent cross-linking of several structural proteins by sulfhydryl oxidases and transglutaminases (TGases). This highly insoluble protein meshwork is coated by the lipid envelope, a ϳ5 nm thick layer of -hydroxyceramides with uniquely long (C 28 -C 36 ) fatty acyl moieties (3). These are covalently attached by ester bonds through their -hydroxyl group to selected glutamines to envoplakin, periplakin, and involucrin components of the protein envelope (4).Terminal differentiation of keratinocytes is accompanied by vigorous lipid metabolism and synthesis of keratinization-specific lipids in the granular layer. Newly synthesized lipids are temporarily stored in cytoplasmic lamellar bodies, in which they are arranged as stacks of tetralaminar sheets. The lamellar body lipids consist largely of free fatty acids, (glucosyl)ceramides, cholesterol, and its acyl or sulfate esters (3). In the uppermost granular layer the lamellar bodies fuse with the cell membrane, and release their contents which assume broad, multilamellar lipid sheets between corneocytes. This process approxima...

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Lipid Composition of Cohesive and Desquamated Corneocytes from Mouse Ear Skin

Cited by 89 publications

References 25 publications

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

Cholesterol sulfate in human physiology: what's it all about?

Cholesterol 3-Sulfate Interferes with Cornified Envelope Assembly by Diverting Transglutaminase 1 Activity from the Formation of Cross-links and Esters to the Hydrolysis of Glutamine

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