| The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages. | |
| | |
MedLine Citation:
|
PMID: 20947831 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
RATIONALE: Hydrolysis of intracellular cholesterol ester (CE) is the key step in the reverse cholesterol transport in macrophage foam cells. We have recently shown that neutral cholesterol ester hydrolase (Nceh)1 and hormone-sensitive lipase (Lipe) are key regulators of this process in mouse macrophages. However, it remains unknown which enzyme is critical in human macrophages and atherosclerosis. OBJECTIVE: We aimed to identify the enzyme responsible for the CE hydrolysis in human macrophages and to determine its expression in human atherosclerosis. METHODS AND RESULTS: We compared the expression of NCEH1, LIPE, and cholesterol ester hydrolase (CES1) in human monocyte-derived macrophages (HMMs) and examined the effects of inhibition or overexpression of each enzyme in the cholesterol trafficking. The pattern of expression of NCEH1 was similar to that of neutral CE hydrolase activity during the differentiation of HMMs. Overexpression of human NCEH1 increased the hydrolysis of CE, thereby stimulating cholesterol mobilization from THP-1 macrophages. Knockdown of NCEH1 specifically reduced the neutral CE hydrolase activity. Pharmacological inhibition of NCEH1 also increased the cellular CE in HMMs. In contrast, LIPE was barely detectable in HMMs, and its inhibition did not decrease neutral CE hydrolase activity. Neither overexpression nor knockdown of CES1 affected the neutral CE hydrolase activity. NCEH1 was expressed in CD68-positive macrophage foam cells of human atherosclerotic lesions. CONCLUSIONS: NCEH1 is expressed in human atheromatous lesions, where it plays a critical role in the hydrolysis of CE in human macrophage foam cells, thereby contributing to the initial part of reverse cholesterol transport in human atherosclerosis. |
| | |
Authors:
|
Masaki Igarashi; Jun-ichi Osuga; Hiroshi Uozaki; Motohiro Sekiya; Shuichi Nagashima; Manabu Takahashi; Satoru Takase; Mikio Takanashi; Yongxue Li; Keisuke Ohta; Masayoshi Kumagai; Makiko Nishi; Masakiyo Hosokawa; Christian Fledelius; Poul Jacobsen; Hiroaki Yagyu; Masashi Fukayama; Ryozo Nagai; Takashi Kadowaki; Ken Ohashi; Shun Ishibashi |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-14 |
Journal Detail:
|
Title: Circulation research Volume: 107 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-25 Completed Date: 2010-12-27 Revised Date: 2011-11-03 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 1387-95 Citation Subset: IM |
Affiliation:
|
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Aged, 80 and over Atherosclerosis / enzymology, metabolism, pathology Biological Transport / physiology Carrier Proteins / biosynthesis, genetics, physiology* Cells, Cultured Cholesterol / metabolism* Female Gene Expression Regulation, Enzymologic Gene Knockdown Techniques / methods HEK293 Cells Humans Macrophages / enzymology*, metabolism Male Middle Aged Monocytes / enzymology, metabolism Serine Proteases / biosynthesis, genetics, physiology* Sterol Esterase / biosynthesis, genetics, physiology* |
| Chemical | |
Reg. No./Substance:
|
0/Carrier Proteins; 57-88-5/Cholesterol; EC 3.1.1.-/Nceh1 protein, mouse; EC 3.1.1.13/Sterol Esterase; EC 3.4.-/Serine Proteases |
| Comments/Corrections | |
Comment In:
|
Circ Res. 2011 May 13;108(10):e13
[PMID:
21566218
]
Circ Res. 2011 Mar 4;108(5):e6-7; author reply e8-e9 [PMID: 21372287 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in ...
Next Document: Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umb...