Document Detail

Ceramides stimulate caspase-14 expression in human keratinocytes.
MedLine Citation:
PMID:  23362869     Owner:  NLM     Status:  MEDLINE    
Caspase-14 is an enzyme that is expressed predominantly in cornifying epithelia and catalyses the degradation of profilaggrin. Additionally, caspase-14 plays an important role in the terminal differentiation of keratinocytes. However, how caspase-14 expression is regulated remains largely unknown. Here we demonstrate that ceramides (C(2) -Cer and C(6) -Cer), but not other sphingolipids (C(8) -glucosylceramides, sphinganine, sphingosine-1-phosphate or ceramide-1-phosphate), increase caspase-14 expression (mRNA and protein) in cultured human keratinocytes in a dose- and time-dependent manner. Inhibitors of glucosylceramide synthase and ceramidase increase endogenous ceramide levels and also increase caspase-14 expression, indicating an important regulatory role for ceramides and suggesting that the conversion of ceramides to other metabolites is not required. The increase in caspase-14 expression induced by ceramides is first seen at 16 h and requires new protein synthesis, suggesting that the ceramide-induced increase is likely an indirect effect. Furthermore, ceramides increase caspase-14 gene expression primarily by increasing transcription. Blocking de novo synthesis of ceramides does not affect caspase-14 expression, suggesting that basal expression is not dependent on ceramide levels. These studies show that ceramides, an important structural lipid, stimulate caspase-14 expression providing a mechanism for coordinately regulating the formation of lipid lamellar membranes with the formation of corneocytes.
Yan J Jiang; Peggy Kim; Yoshikazu Uchida; Peter M Elias; Daniel D Bikle; Carl Grunfeld; Kenneth R Feingold
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Experimental dermatology     Volume:  22     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-31     Completed Date:  2013-08-07     Revised Date:  2014-08-04    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  113-8     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
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MeSH Terms
Caspases / metabolism*
Cells, Cultured
Ceramides / metabolism*
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Enzymologic*
Glucosyltransferases / antagonists & inhibitors
Keratinocytes / enzymology*
Lipids / chemistry
Orphan Nuclear Receptors / metabolism
Peroxisome Proliferator-Activated Receptors / metabolism
Promoter Regions, Genetic
RNA, Messenger / metabolism
Time Factors
Transcriptional Activation
Grant Support
Reg. No./Substance:
0/Ceramides; 0/Enzyme Inhibitors; 0/Lipids; 0/Orphan Nuclear Receptors; 0/Peroxisome Proliferator-Activated Receptors; 0/RNA, Messenger; 0/liver X receptor; EC 2.4.1.-/Glucosyltransferases; EC 3.4.22.-/CASP14 protein, human; EC 3.4.22.-/Caspases

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