Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis.

Elias, Peter M.; Williams, Mary L.; Maloney, Mary E.; Bonifas, J A; Brown, Barbara E.; Grayson, Stephen; Epstein, Ervin

doi:10.1172/jci111552

Cited by 187 publications

(100 citation statements)

References 21 publications

(26 reference statements)

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“…Nevertheless, this estimate of 4.5-5.5% is right in the range found in the lowest layers of normal stratum corneum, and is severalfold less than that measured in XI epidermis (55).…”

Section: Effect Of Slv Content Of Cso 4 On -Hydroxyceramidecontrasting

confidence: 60%

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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“…Nevertheless, this estimate of 4.5-5.5% is right in the range found in the lowest layers of normal stratum corneum, and is severalfold less than that measured in XI epidermis (55).…”

Section: Effect Of Slv Content Of Cso 4 On -Hydroxyceramidecontrasting

confidence: 60%

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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“…Cette enzyme elimine le groupement phosphate de substrats tres varies, elle n'est specifique que de la partie phosphate. [18]. Cette activite hydrolytique a Cte observee pour plusieurs substrats (voir Tableau I).…”

Section: Phosphataseunclassified

Untitled

1992

Intern J of Cosmetic Sci

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SynopsisBien que le stratum corneum soit compose de cellules 'mortes', il est le siege d'une activite metabolique tres importante. Mais, contrairement a la plupart d'autres tissus, cette activite a la particularite d'itre extracellulaire. Elle est due a des enzymes excretees par les Corps d'Odland avec les bicouches ceramidiques.Ces enzymes sont des hydrolases, elles sont identiques ou tres proches de celles des lysosomes. Les principales activites observees correspondent a une (ou des) glycosidase(s), une phospholipase, une sphingomyelinase, une phosphatase, une (ou des) esterase(s), des sulfatases, des proteases. Comme les hydrolases des lysosomes, elles semblent peu specifiques.Ce pool enzymatique pourrait jouer plusieurs rdes fondamentaux, notamment:1. La transformation des bicouches gluco-ceramidiques en bicouches ceramidiques plus lipophiles; 2. Lelimination de la membrane plasmique, dont certains produits du catabolisme, comme les acides gras et 3. La diminution de la cohesion entre les corneocytes; 4. La protection contre I'intrusion de corps etrangers.Comme tout systeme enzymatique, les hydrolases extra-cellulaires. sont certainement soumises a des regulations. Plusieurs de ces regulations sont envisagees.A partir de considerations d'enzymologie, le pH de la base du stratum corneum peut itre estime a environ 5.En cosmetologie, les enzymes du stratum corneum sont mises a contribution pour rendre actifs des L'etude des consequences des modifications de I'activitt enzymatique sur I'Ctat de la peau pourrait constituer les ceramides, peuvent itre integres aux bicouches ceramidiques; precurseurs.une future voie de recherche extrimement prometteuse. RCumeAlthough the stratum corneum is composed of dead cells, it is the site of considerable metabolic activity. However, in contrast with other tissues, their activity is extra-cellular, being due to enzymes excreted by Odland bodies with the ceramide bilayers. These enzymes are generally hydrolases and one finds glycosidase, phospholipase, sphingomyelinase, phosphatase, esterase, sulphatase and protease activity.As for the lysosome hydrolase to which they bear a close resemblance, they are not very specific. The glycosidase hydrolysesB-~-glucose, a-D-glucose, ~-o-galactose and even a-L-fucose. The most important is forb-D-glucoside.The junction between the stratum corneum and the stratum granulosum is important as the site of the ultimate differentiation of keratinosytes. The ceramide bilayers are important for the maintenance and control of transepidermal water loss and are deposited in the extra-cellular space. The bilayers after excretion become more lipophilic and functional after the loss of the glucose, which was bound to the ceramide. The hydrolysis of thep-r, glucosidic link is carried out by the extra-cellular glycosidase. This loss of glucose reduces the polarity of the sphingolipid. 0142- 48 ForestierThe elimination of the cell membrane is probably effected by the phospholipase and the sphingomyelinase. Certain products of these reactions such as fatty...

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“…The increase in cholesterol sulfate has been related to an increase in the enzyme cholesterol sulfotransferase (68). Although a function for the cholesterol sulfate accumulation in the process of squamous differentiation has not been established, it has been suggested that it may play a role in the modulation of lipid metabolism (67)(68)(69) (74,77,78).…”

Section: Clonogenic Tracheobronchial Epithelial Cells Are Pluripotentmentioning

confidence: 99%

Multistep Process of Squamous Differentiation in Tracheobronchial Epithelial Cells In Vitro: Analogy with Epidermal Differentiation

Jetten¹

1989

Environmental Health Perspectives

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The lung, in particular the bronchial epithelium, is a major site for tumor formation in humans. Environmental factors, such as cigarette smoke, in conjunction with genetic factors are important determinants in this disease. Malignant cells exhibit alterations in their control of proliferation and differentiation. It is believed that the acquisition of defects in the regulation of these processes is important in the process of carcinogenesis. A clear insight into the basic mechanisms of the regulation of proliferation and differentiation is required to understand the molecular mechanisms involved in tumor development and in other pathological conditions. Studies using in vitro cell culture systems of tracheobronchial epithelial cells provide useful models in which to study the regulation of differentiation and proliferation. The clonogenic cells derived from the treacheobronchial epithelium are pluripotent: They have self-renewal capacity and can differentiate along either a normal, mucosecretory, or a squamous cell pathway. Squamous differentiation in tracheobronchial epithelial cells has many morphological, biochemical, and regulatory properties in common with epidermal differentiation. This pathway of differentiation is a multistep process consisting of at least three stages. In the initial stage, cells become committed to terminal cell division. This is followed by the expression of the squamous differentiated phenotype and finally cornification. Various factors, such as several growth factors, retinoids, calcium ions, and phorbol esters, regulate the program of differentiation at different stages. Studies have indicated that the controls of proliferation and differentiation are interrelated. Cell lines established from tracheobronchial epithelial cells expressing SV40 large T-antigen, as well as carcinoma cell lines, exhibit altered responses to growth and differentiation regulatory factors Alterations in the commitment to terminal cell division must be a crucial step in the transition of a normal to a malignant cell.

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Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis.

Abstract: Abstract. The pathological scaling in recessive x-linked ichthyosis is associated with accumulation of

Cited by 187 publications

References 21 publications

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

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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Multistep Process of Squamous Differentiation in Tracheobronchial Epithelial Cells In Vitro: Analogy with Epidermal Differentiation

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