| Serine palmitoyltransferase (SPT) deficient mice absorb less cholesterol. | |
| | |
MedLine Citation:
|
PMID: 19416652 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Serine palmitoyltransferase (SPT) is the key enzyme for the biosynthesis of sphingolipids. It has been reported that oral administration of myriocin (an SPT inhibitor) decreases plasma sphingomyelin (SM) and cholesterol levels, and reduces atherosclerosis in apoE knockout (KO) mice. We studied cholesterol absorption in myriocin-treated WT or apoE KO animals and found that, after myriocin treatment, the mice absorbed significantly less cholesterol than controls, with no observable pathological changes in the small intestine. More importantly, we found that heterozygous Sptlc1 (a subunit of SPT) KO mice also absorbed significantly less cholesterol than controls. To understand the mechanism, we measured protein levels of Niemann-Pick C1-like 1 (NPC1L1), ABCG5, and ABCA1, three key factors involved in intestinal cholesterol absorption. We found that NPC1L1 and ABCA1 were decreased, whereas ABCG5 was increased in the SPT deficient small intestine. SM levels on the apical membrane were also measured and they were significantly decreased in SPT deficient mice, compared with controls. In conclusion, SPT deficiency might reduce intestinal cholesterol absorption by altering NPC1L1 and ABCG5 protein levels in the apical membranes of enterocytes through lowering apical membrane SM levels. This may be also true for ABCA1 which locates on basal membrane of enterocytes. Manipulation of SPT activity could thus provide a novel alternative treatment for dyslipidemia. |
| | |
Authors:
|
Zhiqiang Li; Tae-Sik Park; Yan Li; Xiaoyue Pan; Jahangir Iqbal; David Lu; Weiqing Tang; Liqing Yu; Ira J Goldberg; M Mahmood Hussain; Xian-Cheng Jiang |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-01-29 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: 1791 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2009 Apr |
Date Detail:
|
Created Date: 2009-05-08 Completed Date: 2009-06-30 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 297-306 Citation Subset: IM |
Affiliation:
|
Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
ATP-Binding Cassette Transporters
/
genetics,
metabolism Absorption Animals Apolipoproteins E / physiology Blotting, Western Cholesterol / metabolism* Enterocytes / drug effects, metabolism* Enzyme Inhibitors / administration & dosage Fatty Acids, Monounsaturated / administration & dosage Intestinal Absorption* Intestine, Small / metabolism Lipid Metabolism Lipoproteins / genetics, metabolism Male Membrane Transport Proteins / genetics, metabolism Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Serine C-Palmitoyltransferase / antagonists & inhibitors, physiology* Toxins, Biological / pharmacology Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
HL69817/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/ABCG5 protein, mouse; 0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Apolipoproteins E; 0/Enzyme Inhibitors; 0/Fatty Acids, Monounsaturated; 0/Lipoproteins; 0/Membrane Transport Proteins; 0/Npc1l1 protein, mouse; 0/RNA, Messenger; 0/Toxins, Biological; 0/Triglycerides; 0/lysenin; 35891-70-4/thermozymocidin; 57-88-5/Cholesterol; EC 2.3.1.50/Serine C-Palmitoyltransferase; EC 2.3.1.50/Sptlc1 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The lipopolysaccharide transport system of Gram-negative bacteria.
Next Document: Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25-35 fibrillation.