Role of ceramide 1 in the molecular organization of the stratum corneum lipids

Bouwstra, Joke A.; Gooris, Gert S.; Dubbelaar, F.E.R.; Weerheim, Arij; Ijzerman, A. P.; Ponec, Maria

doi:10.1016/s0022-2275(20)34214-0

Cited by 257 publications

(138 citation statements)

References 27 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…For example, only -OH-containing Cer species are covalently attached to cornified envelope proteins, underscoring their putative role in lamellar membrane organization. In addition, one of the -acylated Cer species (Cer 1) has been shown to be an essential component in the formation of the broadnarrow-broad sequence of the lamellar membrane unit structure (67). The present study supports the hypothesis that the majority of SC Cer 1 is derived from acylGlcCer hydrolysis, rather than from SM precursors (15,68,69).…”

Section: Discussionsupporting

confidence: 85%

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides

Uchida

Hara²,

Nishio³

et al. 2000

Journal of Lipid Research

193

View full text Add to dashboard Cite

Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique -hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of ␤ -glucocerebrosidase. Using gas chromatographymass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked ( N -acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C 22-26 ), short-chain FA (SM-2; primarily C 16 ), and short-chain ␣ -hydroxy FA (SM-3; C 16-18 ). In contrast, only trace quantities of -hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the -hydroxy Cer species, do not derive from SM.

show abstract

Section: Discussionsupporting

confidence: 85%

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides

Uchida

Hara²,

Nishio³

et al. 2000

Journal of Lipid Research

193

View full text Add to dashboard Cite

show abstract

“…Some ceramides have a known particular function in preventing the excess water loss. Ceramide 1, for example, containing linoleic acid ester-linked to a long chain w-hydroxy fatty acid, seems to have a critical function in the molecular arrangement of the stratum corneum lamellar lipid bilayer formation (Bouwstra et al, 1998), and in the assembly and organization of the intercellular space of the stratum corneum (Wertz and Downing, 1983;Bowser et al, 1985). Other ceramides characterized by fatty acid and sphingosine chains of varying size are covalently bound to involucrin and other structural proteins of corni®ed cell envelopes in terminally differentiated keratinocytes and form a hydrophobic milieu on the surface of the cell (Marekov and Steinert, 1998).…”

Section: Discussionmentioning

confidence: 99%

The Level of Prosaposin is Decreased in the Skin of Patients with Psoriasis Vulgaris

Alessandrini

Stachowitz

Ring

et al. 2001

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Ceramides are the most abundant lipids constituting the intercellular matrix of the skin stratum corneum and their critical role in skin homeostasis has been extensively documented. Their concentration in the skin highly depends on the rate of availability of the enzymes involved in ceramide generation. The aim of this study was to investigate whether the concentration of prosaposin was altered in the skin of patients with psoriasis vulgaris. Prosaposin, the precursor of saposins (sphingolipid activator proteins), was measured in lesional and nonlesional skin of psoriatic patients and in normal skin from surgical patients, both at the mRNA and at the protein level. Densitometric analysis of reverse transcriptase-polymerase chain reaction bands separated by gel-electrophoresis showed a progressive decrease of prosaposin mRNA expression in nonlesional and lesional psoriatic skin, being substantially decreased in lesional psoriatic skin compared with normal control skin. Immunohistochemical analysis showed a significant decrease of prosaposin level in the stratum corneum of psoriatic lesional skin (both in active-type and in chronic-type plaque) compared with nonlesional and with normal skin (p < 0.01), and in psoriatic nonlesional skin compared with normal control (p < 0.05). Immunolocalization of sphingomyelinase in lesional and nonlesional psoriatic skin showed a decrease in the level of this enzyme in the stratum corneum of psoriatic lesional, compared with nonlesional skin. These results support the concept that disturbance of epidermal barrier function caused by derangement in ceramide generation can be crucial for the development of psoriatic skin diseases.

show abstract

“…Furthermore, in mouse and human SC the lipids are predominantly organized in an orthorhombic lateral sublattice (White et al, 1988;Garson et al, 1991;Bouwstra et al, 1992Bouwstra et al, , 1994, whereas in pig SC the lipids are in a hexagonal sublattice (Bouwstra et al, 1995). As the 13 nm phase is present in all examined species and is of an unusual lipid arrangement (Swartzendruber, 1992;Bouwstra et al, 1998a), this phase has been considered to be very important for the permeability barrier of the skin.…”

mentioning

confidence: 99%

Phase Behavior of Stratum Corneum Lipid Mixtures Based on Human Ceramides: The Role of Natural and Synthetic Ceramide 1

Bouwstra

Gooris

Dubbelaar

et al. 2002

Journal of Investigative Dermatology

145

View full text Add to dashboard Cite

In a recent study the lipid phase behavior of mixtures of human ceramides, cholesterol, and free fatty acids has been examined. We observed in cholesterol: human ceramide mixtures a prominent formation of the 12.8 nm lamellar phase (referred to as the long periodicity phase). Addition of free fatty acids promoted the formation of a 5.6 nm lamellar phase (referred to as the short periodicity phase) and increased the subpopulation of lipids forming a fluid phase. In this study we focused on the role of human ceramide 1, as the presence of this ceramide appeared to be crucial for proper lipid phase behavior in mixtures prepared with ceramide isolated from pig stratum corneum. In order to do this, mixtures of cholesterol and free fatty acids were prepared with human ceramides, in which natural human ceramide 1 was replaced by either synthetic CER1-linoleate (CER1-lin), or CER1-oleate (CER1-ol), or CER1-stearate (CER1-ste). After substitution of natural human ceramide 1 by synthetic ceramide 1 the following observations were made. (i) In the presence of synthetic CER1-ste no long periodicity phase and no liquid phase could be detected. (ii) In the presence of HCER1-ol a liquid phase was more prominently formed than in the presence of HCER1-lin. (iii) In cholesterol:human ceramide mixtures in the presence of CER1-lin the long periodicity phase was more prominently present than in the presence of CER1-ol. (iv) In the presence of CER1-ste neither a long periodicity phase nor a liquid lateral packing could be detected. The results of these studies further indicate that for the formation of the long periodicity phase a certain (optimal) fraction of lipids has to form a liquid phase. When the fraction forming this liquid phase is either too low or too high, the formation of the short periodicity phase is increased at the expense of the formation of the long periodicity phase. Based on the results of this and previous studies we offer an explanation for the deviation in lipid organization in diseased and in dry skin compared to normal skin.

show abstract

Role of ceramide 1 in the molecular organization of the stratum corneum lipids

Cited by 257 publications

References 27 publications

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides

The Level of Prosaposin is Decreased in the Skin of Patients with Psoriasis Vulgaris

Phase Behavior of Stratum Corneum Lipid Mixtures Based on Human Ceramides: The Role of Natural and Synthetic Ceramide 1

Contact Info

Product

Resources

About