| Catabolism of 4-hydroxy-2-trans-nonenal by THP1 monocytes/macrophages and inactivation of carboxylesterases by this lipid electrophile. | |
| | |
MedLine Citation:
|
PMID: 21878322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oxidative stress in cells and tissues leads to the formation of an assortment of lipid electrophiles, such as the quantitatively important 4-hydroxy-2-trans-nonenal (HNE). Although this cytotoxic aldehyde is atherogenic the mechanisms involved are unclear. We hypothesize that elevated HNE levels can directly inactivate esterase and lipase activities in macrophages via protein adduction, thus generating a biochemical lesion that accelerates foam cell formation and subsequent atherosclerosis. In the present study we examined the effects of HNE treatment on esterase and lipase activities in human THP1 monocytes/macrophages at various physiological scales (i.e., pure recombinant enzymes, cell lysate, and intact living cells). The hydrolytic activities of bacterial and human carboxylesterase enzymes (pnbCE and CES1, respectively) were inactivated by HNE in vitro in a time- and concentration-dependent manner. In addition, so were the hydrolytic activities of THP1 cell lysates and intact THP1 monocytes and macrophages. A single lysine residue (Lys105) in recombinant CES1 was modified by HNE via a Michael addition reaction, whereas the lone reduced cysteine residue (Cys389) was found unmodified. The lipolytic activity of cell lysates and intact cells was more sensitive to the inhibitory effects of HNE than the esterolytic activity. Moreover, immunoblotting analysis using HNE antibodies confirmed that several cellular proteins were adducted by HNE following treatment of intact THP1 monocytes, albeit at relatively high HNE concentrations (>50μM). Unexpectedly, in contrast to CES1, the treatment of a recombinant human CES2 with HNE enhanced its enzymatic activity ∼3-fold compared to untreated enzyme. In addition, THP1 monocytes/macrophages can efficiently metabolize HNE, and glutathione conjugation of HNE is responsible for ∼43% of its catabolism. The functional importance of HNE-mediated inactivation of cellular hydrolytic enzymes with respect to atherogenesis remains obscure, although this study has taken a first step toward addressing this important issue by examining the potential of HNE to inhibit this biochemical activity in a human monocyte/macrophage cell line. |
| | |
Authors:
|
Abdolsamad Borazjani; Mariola J Edelmann; Katelyn L Hardin; Katye L Herring; J Allen Crow; Matthew K Ross |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-22 |
Journal Detail:
|
Title: Chemico-biological interactions Volume: 194 ISSN: 1872-7786 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-04 Completed Date: 2011-11-15 Revised Date: 2013-05-23 |
Medline Journal Info:
|
Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
|
Languages: eng Pagination: 1-12 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
|
Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aldehydes
/
metabolism,
pharmacology* Atherosclerosis / metabolism, pathology Carboxylic Ester Hydrolases / antagonists & inhibitors*, metabolism Cell Line Cysteine Proteinase Inhibitors / metabolism, pharmacology* Dose-Response Relationship, Drug Enzyme Activation / drug effects Humans Inflammation / metabolism, pathology Lipid Metabolism / drug effects Macrophages / cytology, drug effects*, metabolism Monocytes / cytology, drug effects*, metabolism Time Factors |
| Grant Support | |
ID/Acronym/Agency:
|
1R15ES015348/ES/NIEHS NIH HHS; R15 ES015348-01A1/ES/NIEHS NIH HHS; R15 ES015348-01A1S1/ES/NIEHS NIH HHS; R15 ES015348-01A1S2/ES/NIEHS NIH HHS; T35RR007071/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Aldehydes; 0/Cysteine Proteinase Inhibitors; 29343-52-0/4-hydroxy-2-nonenal; EC 3.1.1.-/Carboxylic Ester Hydrolases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype.
Next Document: Relative exchangeable copper: A new highly sensitive and highly specific biomarker for Wilson's dise...