Abstract
A deficiency of ordinary ceramides in the stratum corneum is an essential etiologic
factor for the dry and barrier-disrupted skin of patients with atopic dermatitis (AD).
We have proposed that the mechanism underlying that deficiency involves a novel sphingolipid
metabolizing enzyme, termed sphingomyelin (SM) glucosylceramide (GCer) deacylase,
which hydrolyzes SM or GCer at the acyl site to yield their lysoforms sphingosylphosphorylcholine
(SPC) or glucosylsphingosine (GSP) instead of ceramide, leading to the ceramide deficiency
in the AD skin. The enzymic characteristics observed showed a pH dependency of catalytic
activity with a peak at pH 5.0 and a molecular weight of 40,000. Analytical isoelectric
focusing (IEF) chromatography demonstrated that the pI values of SM deacylase, GlcCDase, SMase and ceramidase were 4.2, 7.4, 7.0 and 5.7,
respectively. Those enzymic characteristics of SM-GCer deacylase are completely distinct
from ceramidase as well as the other known deacylases. Our enzymic measurements demonstrated
that SM-GCer deacylase activity is enhanced more than 5-fold in involved stratum corneum,
more than 3-fold in uninvolved stratum corneum and approximately 3-fold in the involved
epidermis from patients with AD compared with healthy controls. Our findings suggest
that the novel enzyme, SM-GCer deacylase, is expressed in situ at significant levels
in the epidermis of AD patients. This results in the production of SPC and GSP, instead
of ceramides, which leads in turn to the ceramide deficiency seen in the stratum corneum
of those patients. It is likely that the biogenesis of SM-GCer deacylase may be critical
to the pathogenesis of AD.
Abbreviations:
AD (atopic dermatitis), CDase (ceramidase), GlcCDaseβ (-glucocerebrosidase), GCer (glucosylceramide), GC (glucosylceramide), GSP (glucosylsphingosine), IEF (isoelectric focusing), PC (phosphorylcholine), SM (sphingomyelin), SMase (sphingomyelinase), SS (sphingosine), SPC (sphingosylphosphorylcholine), TLC (thin layer chromatography), TEWL (transepidermal water loss)Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
April 16,
2009
Received in revised form:
April 15,
2009
Received:
February 5,
2009
Identification
Copyright
© 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
