Document Detail


Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy.
MedLine Citation:
PMID:  17052686     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sphingolipids are comprised of a backbone sphingoid base that may be phosphorylated, acylated, glycosylated, bridged to various headgroups through phosphodiester linkages, or otherwise modified. Organisms usually contain large numbers of sphingolipid subspecies and knowledge about the types and amounts is imperative because they influence membrane structure, interactions with the extracellular matrix and neighboring cells, vesicular traffic and the formation of specialized structures such as phagosomes and autophagosomes, as well as participate in intracellular and extracellular signaling. Fortunately, "sphingolipidomic" analysis is becoming feasible (at least for important subsets such as all of the backbone "signaling" subspecies: ceramides, ceramide 1-phosphates, sphingoid bases, sphingoid base 1-phosphates, inter alia) using mass spectrometry, and these profiles are revealing many surprises, such as that under certain conditions cells contain significant amounts of "unusual" species: N-mono-, di-, and tri-methyl-sphingoid bases (including N,N-dimethylsphingosine); 3-ketodihydroceramides; N-acetyl-sphingoid bases (C2-ceramides); and dihydroceramides, in the latter case, in very high proportions when cells are treated with the anticancer drug fenretinide (4-hydroxyphenylretinamide). The elevation of DHceramides by fenretinide is befuddling because the 4,5-trans-double bond of ceramide has been thought to be required for biological activity; however, DHceramides induce autophagy and may be important in the regulation of this important cellular process. The complexity of the sphingolipidome is hard to imagine, but one hopes that, when partnered with other systems biology approaches, the causes and consequences of the complexity will explain how these intriguing compounds are involved in almost every aspect of cell behavior and the malfunctions of many diseases.
Authors:
Wenjing Zheng; Jessica Kollmeyer; Holly Symolon; Amin Momin; Elizabeth Munter; Elaine Wang; Samuel Kelly; Jeremy C Allegood; Ying Liu; Qiong Peng; Harsha Ramaraju; M Cameron Sullards; Myles Cabot; Alfred H Merrill
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2006-08-22
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1758     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-13     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1864-84     Citation Subset:  IM    
Affiliation:
School of Biology, Chemistry and Biochemistry, Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
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MeSH Terms
Descriptor/Qualifier:
Autophagy*
Ceramides / physiology*
Disease
Humans
Hydrolysis
Molecular Structure
Signal Transduction*
Sphingolipids / chemistry,  metabolism,  physiology*
Subcellular Fractions / metabolism
Grant Support
ID/Acronym/Agency:
GM069338/GM/NIGMS NIH HHS; U19-CA87525/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Ceramides; 0/Sphingolipids

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


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