Document Detail


Hydrolytic pathway protects against ceramide-induced apoptosis in keratinocytes exposed to UVB.
MedLine Citation:
PMID:  20520628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although ceramides (Cers) are key constituents of the epidermal permeability barrier, they also function as apoptogenic signals for UVB irradiation-induced apoptosis in epidermal keratinocytes. As epidermis is continuously exposed to UV irradiation, we hypothesized that Cer hydrolysis protects keratinocytes from UVB-induced apoptosis by attenuating Cer levels. Both low-dose UVB (L-UVB) (< 35 mJ cm(-2)) and high-dose UVB (H-UVB) (> or = 45 mJ cm(-2)) irradiation inhibited DNA synthesis in cultured human keratinocytes, but apoptosis occurred only after H-UVB. Whereas Cer production increased after both L- and H-UVB, it normalized only in L-UVB-exposed keratinocytes, but remained elevated after H-UVB. Both acidic ceramidase (aCDase) and neutral ceramidase (nCDase) activities declined after L- and H-UVB, but returned to normal only in L-UVB cells, with decreased CDase activities or mRNA or protein levels being sustained in H-UVB cells. Inhibition of CDase using either a CDase inhibitor, N-oleoylethanolamine, or small interfering RNA (siRNA) (either to a- and/or n-CDase(s)) sensitized keratinocytes to L-UVB-induced apoptosis in parallel with further Cer accumulation. Blockade of sphingosine kinase 1 (SPHK1) (but not SPHK2) by siRNA also increased apoptosis in L-UVB keratinocytes, revealing that conversion of sphingosine to sphingosine-1-phosphate (S1P) further protects keratinocytes from UVB-induced cell death. Thus, Cer → sphingosine → S1Pmetabolic conversion protects against UVB-induced, Cer-mediated apoptosis in keratinocytes, but excessive UVB overwhelms this mechanism, thereby leading to keratinocyte apoptosis.
Authors:
Yoshikazu Uchida; Evi Houben; Kyungho Park; Sounthala Douangpanya; Yong-Moon Lee; Bill X Wu; Yusuf A Hannun; Norman S Radin; Peter M Elias; Walter M Holleran
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-03
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  130     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-15     Completed Date:  2010-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2472-80     Citation Subset:  IM    
Affiliation:
Department of Dermatology, School of Medicine, University of California, San Francisco, San Francisco, California, USA. uchiday@derm.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Acid Ceramidase / genetics,  metabolism*
Apoptosis* / drug effects,  physiology,  radiation effects
Cells, Cultured
Ceramides / toxicity
Cytoprotection / drug effects
Gene Expression Regulation, Enzymologic / radiation effects
Humans
Hydrolysis
Keratinocytes* / cytology,  drug effects,  radiation effects
Neutral Ceramidase / genetics,  metabolism*
Phosphotransferases (Alcohol Group Acceptor) / genetics,  metabolism*
RNA, Messenger / metabolism
RNA, Small Interfering
Signal Transduction / drug effects,  radiation effects
Sphingosine / metabolism
Ultraviolet Rays / adverse effects*
Grant Support
ID/Acronym/Agency:
AI059311/AI/NIAID NIH HHS; AR051077/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Ceramides; 0/RNA, Messenger; 0/RNA, Small Interfering; 123-78-4/Sphingosine; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase; EC 3.5.1.23/Acid Ceramidase; EC 3.5.1.23/Neutral Ceramidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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