Abstract
Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-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 beta-glucocerebrosidase. Using gas chromatography-mass 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 alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-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 omega-hydroxy Cer species, do not derive from SM.
Highlights
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
Epidermal phospholipids contained three high performance thin-layer chromatography (HPTLC) bands; that is, with Rf values of 0.19 (SM-3), 0.23 (SM-2), and 0.27 (SM-1) (Fig. 1A, lane 2) that correspond to authentic SM
Whereas the three SM components in the phospholipid fraction were hydrolyzed to three Cer species (i.e., Cer-A, Cer-B, and Cer-C; Fig. 1B, lane 3), other phospholipid components [e.g., phosphatidylethanolamine (PE) and phosphatidylcholine (PC)] remained unaltered by sphingomyelinase treatment (Fig. 1A, lane 3)
Summary
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. A large, additional pool of secreted Cer, in combination with cholesterol and free fatty acids (FA), form extracellular lamellar membrane structures within the stratum corneum (SC) that subserve the permeability barrier to water loss, necessary for the survival of mammals in a terrestrial environment [3] These extracellular Cer comprise ϳ50% of the SC lipids [4, 5], and represent a heterogeneous family of at least seven molecules, with variations in the long-chain sphingoid base structure, as well as in the chain length and ␣-hydroxylation of constituent amide-linked FA [6,7,8]. These studies suggest that SM-derived Cer are important for permeability barrier homeostasis
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