Human Epidermal Glucosylceramides are Major Precursors of Stratum Corneum Ceramides.

Hamanaka, Sumiko; Hara, Mariko; Nishio, Hiroyuki; Otsuka, Fujio; Suzuki, Akemi; Uchida, Yoshikazu

Ceramides are the major component of the stratum corneum, accounting for 30%-40% of stratum corneum lipids by weight, and are composed of at least seven molecular groups (designated ceramides 1–7). Stratum corneum ceramides, together with cholesterol and fatty acids, form extracellular lamellae that are responsible for the epidermal permeability barrier. Previous studies indicated that β-glucocerebrosidase- and sphingomyelinase-dependent ceramide production from glucosylceramides and sphingomyelins, respectively, is important for epidermal permeability barrier homeostasis. A recent study indicated that sphingomyelins are precursors of two stratum corneum ceramide molecular groups (ceramides 2 and 5). In this study, we have examined the role of glucosylceramides in the generation of each of the seven stratum corneum ceramide molecular groups. First, the structures of various glucosylceramide species in human epidermis were determined by gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance. The results indicate that total epidermal glucosylceramides are composed of six distinct molecular groups, glucosylceramides 1–6. Glucosylceramide 1 contains sphingenine and nonhydroxy fatty acids, glucosylceramide 2, phytosphingosine and nonhydroxy fatty acids, glucosylceramide 3, phytosphingosine with one double bond and nonhydroxy fatty acids, glucosylceramide 4, sphingenine and α-hydroxy fatty acids, glucosylceramide 5, phytosphingosine and α-hydroxy fatty acids, and glucosylceramide 6, phytosphingosine with one double bond and α-hydroxy fatty acids. The nonhydroxy fatty acids typically have 16–24-carbon-length chains, whereas α-hydroxy fatty acids are limited to 24-, 25-, and 26-carbon chains. The sphingosine bases are C18 or C20 chains. Next, acylglucosylceramides and glucosylceramides were treated with β-glucocerebrosidase and the ceramides released were compared...

GLYCOSPHINGOLIPIDS; EPIDERMIS

Journal of Investigative Dermatology, 2002, Vol 119, Issue 2, p416

0022-202X

Academic Journal

10.1046/j.1523-1747.2002.01836.x