Document Detail


Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjögren-Larsson syndrome.
MedLine Citation:
PMID:  17971613     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder characterized by ichthyosis, mental retardation, spasticity, and deficient activity of fatty aldehyde dehydrogenase (FALDH). FALDH is an enzyme component of fatty alcohol:NAD oxidoreductase (FAO), which is necessary for fatty alcohol metabolism. To better understand the biochemical basis for the cutaneous symptoms in this disease, we investigated lipid metabolism in cultured keratinocytes from SLS patients. Enzyme activities of FALDH and FAO in SLS cells were <10% of normal. SLS keratinocytes accumulated 45-fold more fatty alcohol (hexadecanol, octadecanol, and octadecenol) than normal, whereas wax esters and 1-O-alkyl-2,3-diacylglycerols were increased by 5.6-fold and 7.5-fold, respectively. SLS keratinocytes showed a reduced incorporation of radioactive octadecanol into fatty acid (24% of normal) and triglyceride (13% of normal), but incorporation into wax esters and 1-O-alkyl-2,3-diacylglycerol was increased by 2.5-fold and 2.8-fold, respectively. Our results indicate that FALDH deficiency in SLS keratinocytes causes the accumulation and diversion of fatty alcohol into alternative biosynthetic pathways. The striking lipid abnormalities in cultured SLS keratinocytes are distinct from those seen in fibroblasts and may be related to the stratum corneum dysfunction and ichthyosis in SLS.
Authors:
William B Rizzo; Debra A Craft; Tara Somer; Gael Carney; Juliana Trafrova; Marcia Simon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-10-30
Journal Detail:
Title:  Journal of lipid research     Volume:  49     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-17     Completed Date:  2008-04-22     Revised Date:  2011-07-26    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  410-9     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA. wrizzo@unmc.edu
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Aldehyde Oxidoreductases / deficiency,  genetics
Animals
Cells, Cultured
Cholesterol Esters / metabolism
Diglycerides / analysis,  chemistry,  metabolism
Fatty Alcohols / chemistry,  metabolism*
Gas Chromatography-Mass Spectrometry
Humans
Keratinocytes / enzymology,  metabolism*,  pathology
Mice
Sjogren-Larsson Syndrome / enzymology,  genetics,  metabolism*,  pathology*
Waxes / metabolism
Grant Support
ID/Acronym/Agency:
AR 44552/AR/NIAMS NIH HHS; P20 RR 016469/RR/NCRR NIH HHS; R01 AR044552-12/AR/NIAMS NIH HHS; R01 AR044552-13/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol Esters; 0/Diglycerides; 0/Fatty Alcohols; 0/Waxes; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.48/long-chain-aldehyde dehydrogenase
Comments/Corrections

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