Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions

Hutchins, Patrick M.; Moore, Ernest E.; Murphy, Robert C.

doi:10.1194/jlr.m019174

Cited by 72 publications

(108 citation statements)

References 56 publications

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“…A recent study showed that SOAT2 KO versus WT mice or mice fed FO versus monounsaturated fat had plasma LDL enriched in PUFA CE species and bound with less affi nity to proteoglycans, suggesting a mechanism by which apoB lipoproteins from mice fed dietary PUFA may be less atherogenic ( 51 ). Although PUFA lipid species are more easily oxidized than their saturated and monounsaturated counterparts ( 52,53 ) and ox-CE species have been identifi ed in human tissue samples from endarterectomies ( 28 ), no arterial ox-CEs were detected in our study, despite signifi cant enrichment of circulating and tissue lipids with by guest, on www.jlr.org Downloaded from large decrease in hepatic TG content does not necessarily result in decreased TG secretion. For example, knockdown of SCD-1 with a targeting anti-sense oligonucleotide resulted in a >90% reduction in hepatic TG content, but did not affect hepatic TG secretion compared with mice treated with a nontargeting anti-sense oligonucleotide ( 66 ).…”

Section: Downloaded Frommentioning

confidence: 99%

“…Human atheromas contain several distinct families of ox-CE species derived from PUFAs (e.g., 18:2 n-6, 20:4 n-6, and 22:6 n-3) that may play a role in atherogenesis ( 28 ). Because three of the four ADs showed substantial PUFA enrichment, we examined ox-CE content in mouse aortas after 16 weeks of AD feeding.…”

Section: Mouse Aortas Lack Ox-ce Speciesmentioning

confidence: 99%

“…Before analysis, the organic layer was dried under N 2 . The residue was then weighed and diluted to 1 g/ l with isooctane, and stored at Ϫ 20°C until analysis of oxidized CE (ox-CE) using LC/MS (/MS) ( 28 ). The remaining 1 ml of the original aortic extract in 75:25 isooctane:ethyl acetate was used to quantify aortic total cholesterol (TC) and FC content by GLC ( 17 ).…”

Section: Pufa-mediated Atheroprotection and Hepatoprotection In Micementioning

confidence: 99%

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Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver

Shewale

Boudyguina

Zhu

et al. 2015

Journal of Lipid Research

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Section: Downloaded Frommentioning

confidence: 99%

Section: Mouse Aortas Lack Ox-ce Speciesmentioning

confidence: 99%

Section: Pufa-mediated Atheroprotection and Hepatoprotection In Micementioning

confidence: 99%

See 1 more Smart Citation

Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver

Shewale

Boudyguina

Zhu

et al. 2015

Journal of Lipid Research

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“…HPLC grade reagents were purchased from Sigma-Aldrich, St. Louis, MO. Neutral lipid extraction was adapted from Hutchins et al ( 48,49 ), and pentafl uorobenzyl derivatization was according to Zarini et al ( 50 ). Mouse milk was thawed at 37°C for 10 min, vortexed, and 5 l of whole milk was transferred to 2 ml Eppendorf tubes containing 0.5 ml of 2:1 v/v methanol/ water; samples were acidifi ed with 40 l of 1M HCL, vortexed into solution, cleared by centrifugation at 10,000 g , and supernatant was transferred into borosilicate glass tubes.…”

Section: Milk Fat and Fatty Acid Composition Analysismentioning

confidence: 99%

Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthase in lactating mammary epithelium

Rudolph

Wellberg

Lewis

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.orgMammalian cells manufacture fatty acids de novo using a distinct pathway to synthesize fatty acids from acetyl and malonyl esters of CoA catalyzed by the dimer of FASN (EC 2.3.1.85) ( 1 ). FASN is absolutely essential for production of de novo fatty acids in mammals ( 2 ). The biological requirement for FASN is highlighted by the fact that FASN is detected in most normal human tissues and that homozygous deletion of FASN in the mouse results in embryonic lethality ( 3, 4 ). The importance of the de novo pathway is underscored by the complex biological functions of its fatty acid products, including biosynthesis of phospholipids, energy storage via esterifi cation into triglycerides (TAGs), use as energy substrates for ␤ -oxidation, providing both endocrine and nuclear hormone signaling ligands, and for critical posttranslational modifi cations of proteins ( 5-12 ). Perhaps the most demanding setting for FASN catalysis is during lactation, when extremely high quantities of de novo fatty acids are transmitted to the offspring as substrate for the growth of the young ( 13-15 ).Regulation of the principle enzymes of de novo fatty acid synthesis, ATP citrate lyase (ACLY) (EC 2.3.3.8), acetyl-CoA carboxylase (ACC) (EC 6.4.1.2), and FASN, has been shown to occur at the level of enzyme gene expression ( 16 ), translation/degradation ( 17-19 ), phosphorylation ( 20-22 ), assembly into multimeric complexes ( 23-25 ), and allosteric activation/inhibition ( 18,23,26,27 ). Recently, evidence for the control of de novo fatty acid synthesis by small effector proteins has emerged. Thyroid hormone responsive protein "Spot 14" (THRSP) (Spot14, S14) and only family Abstract Thyroid hormone responsive protein Spot 14 has been consistently associated with de novo fatty acid synthesis activity in multiple tissues, including the lactating mammary gland, which synthesizes large quantities of medium chain fatty acids (MCFAs) exclusively via FASN. However, the molecular function of Spot14 remains undefi ned during lactation. Spot14-null mice produce milk defi cient in total triglyceride and de novo MCFA that does not sustain optimal neonatal growth. The lactation defect was rescued by provision of a high fat diet to the lactating dam. Transgenic mice overexpressing Spot14 in mammary epithelium produced total milk fat equivalent to controls, but with significantly greater MCFA. Spot14-null dams have no diminution of metabolic gene expression, enzyme protein levels, or intermediate metabolites that accounts for impaired de novo MCFA. When

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“…Neutral lipids were extracted as previously described using 75:25 (v/v) isooctane:ethyl acetate ( 17 ). Phospholipids were extracted with a modifi ed Bligh and Dyer procedure replacing chloroform with dichloromethane ( 19 ).…”

Section: Lipid Extractionsmentioning

confidence: 99%

Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation of oxidized phosphatidylcholine

Hutchins

Murphy

2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org abundant in human blood being cholesteryl esters of linoleate [CE(18:2)], arachidonate [CE(20:4)], and docosahexaenoate [CE(22:6)], all polyunsaturated fatty acids ( 1 ). Intracellular CE is stored in unique organelles called lipid bodies, which consist of a neutral lipid core (CEs and triacylglycerides) surrounded by an amphipathic monolayer chiefl y comprised of phosphatidylcholine (PC) ( 2 ). In the circulation, CEs are concentrated in LDL, which deliver cholesterol to extrahepatic cells through recognition by the LDL receptor at the plasma membrane of target cells followed by endocytosis. Thus, CEs constitute the storage and transport form of cholesterol as well as sequester fatty acids for energy storage. Generally, discussions of CE metabolism are limited to esterifi cation and deesterification, as part of the intercellular CE cycle or during lipoprotein formation and metabolism ( 3, 4 ). However, there has been heightened interest in CE oxidation since in vitro studies revealed that CE(18:2) within LDL was converted to cholesteryl 13( S )-hydroxy-9,11-octadecadienoic acid [CE(13( S )-HODE)] by purifi ed rabbit reticulocyte 15-LO after reduction of the initial hydroperoxide product, cholesteryl 13( S )-hydroperoxy-9,11-octadecadienoic acid [CE(13( S )-HpODE)] ( 5 ). The vast majority of CE oxidation studies have examined the potential role of 15-LO in the generation oxidized LDL, and there is now substantial evidence that 15-LO expression contributes to the oxidation of LDL particles during coincubations with cultured cells ( 6, 7 ). In several of these studies, concurrent CE

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Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions

Cited by 72 publications

References 56 publications

Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver

Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver

Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthase in lactating mammary epithelium

Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation of oxidized phosphatidylcholine

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