Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis.
To clarify the functional relevance of sphingomyelin (SM) deacylase to the ceramide deficiency seen in atopic dermatitis (AD), we developed a new highly sensitive method and measured the metabolic intermediate sphingosylphosphorylcholine (SPC) that accumulates in the stratum corneum. SPC in intercellular lipids extracted from stratum corneum was reacted with [(14)C]acetic anhydride to yield [(14)C-C(2)]SM, which was then analyzed by TLC. In both the lesional and non-lesional stratum corneum obtained from patients with AD, there was a significant increase in the content of SPC over that of healthy control subjects. There was a reciprocal relationship between increases in SPC and decreases in ceramide levels of stratum corneum obtained from healthy controls, and from lesional and non-lesional skin from patients with AD. Comparison with other sphingolipids present in the stratum corneum demonstrated that there is a significant positive correlation between SPC and glucosylsphingosine, another lysosphingolipid derived from glucosylceramide by another novel epidermal enzyme, termed glucosylceramide deacylase. In contrast, there was no correlation between SPC and sphingosine, a degradative product generated from ceramide by ceramidase. These findings strongly suggest the physiological relevance of SM deacylase function in vivo to the ceramide deficiency found in the skin of patients with AD.
Okamoto
Reiko
R
Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
Arikawa
Junko
J
Ishibashi
Mutsumi
M
Kawashima
Makoto
M
Takagi
Yutaka
Y
Imokawa
Genji
G
D000293:Adolescent; D000328:Adult; D002518:Ceramides / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism*; D011609:Psychosine / Q000031:analogs & derivatives; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D015854:Up-Regulation
D002518:Ceramides; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D011609:Psychosine; C035742:sphingosyl beta-glucoside; D013110:Sphingosine