Abstract：
:Lipid modifications aid in regulating (and misregulating) protein function and localization. However, efficient methods to screen for a lipid's ability to modify proteins are not readily available. We present a strategy to identify protein-reactive lipids and apply it to a neurodevelopmental disorder, Smith-Lemli-Opitz syndrome (SLOS). Alkynyl surrogates were synthesized for polyunsaturated fatty acids, phospholipids, cholesterol, 7-dehydrocholesterol (7-DHC), and a 7-DHC-derived oxysterol. To probe for protein-reactive lipids, we used click chemistry to biotinylate the alkynyl tag and detected the lipid-adducted proteins with streptavidin Western blotting. In Neuro2a cells, the trend in amount of protein adduction followed known rates of lipid peroxidation (7-DHC > arachidonic acid > linoleic acid > cholesterol), with alkynyl-7-DHC producing the most adduction among alkynyl lipids. 7-DHC reductase-deficient cells, which cannot properly metabolize 7-DHC, exhibited significantly more alkynyl-7-DHC-protein adduction than control cells. Model studies demonstrated that a 7-DHC peroxidation product covalently modifies proteins. We hypothesize that 7-DHC generates electrophiles that can modify the proteome, contributing to SLOS's complex pathology. These probes and methods would allow for analysis of lipid-modified proteomes in SLOS and other disorders exhibiting 7-DHC accumulation. More broadly, the alkynyl lipid library would facilitate exploration of lipid peroxidation's role in specific biological processes in numerous diseases.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Windsor K,Genaro-Mattos TC,Kim HY,Liu W,Tallman KA,Miyamoto S,Korade Z,Porter NAdoi
10.1194/jlr.M041061subject
Has Abstractpub_date
2013-10-01 00:00:00pages
2842-50issue
10eissn
0022-2275issn
1539-7262pii
jlr.M041061journal_volume
54pub_type
杂志文章abstract：:Four different lipolytic preparations have been isolated from rat skeletal muscle. Two of these, provisionally designated monopalmitin lipase (MPL) and monomyristin lipase (MML), are associated with insoluble cellular particulate fractions. The other two enzymes, provisionally designated tricaproin lipase (TCL) and mo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-03-01 00:00:00
abstract：:The hepatic synthesis of sterol was measured in the male Mongolian gerbil (Meriones unguiculatus) in vivo following the administration of [3H]water by monitoring the incorporation of radioactivity into digitonin-precipitable sterol. A diurnal rhythm in cholesterol synthesis was exhibited under conditions of ad libitum...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:It was postulated that specialized microdomains of the plasma membrane, consistent with caveolae, might play a role in cholesterol trafficking in intestinal cells. The existence, therefore, of caveolin and the role of detergent-resistant microdomains of the plasma membrane in cholesterol trafficking were investigated ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200386-jlr200
更新日期：2002-12-01 00:00:00
abstract：:Isolated rat livers were perfused at 37 degrees C with blood-free, defined medium containing delipidized bovine serum albumin (BSA), BSA-oleate, or BSA-palmitate. Very low density lipoproteins (VLDL) were isolated from the perfusate at 12 degrees C and lipid components were extracted and purified. Differential scannin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Normal human plasma HDL was applied to a column of heparin-Sepharose in the presence of MnCl(2) and three fractions were obtained by stepwise elution with increasing NaCl concentrations: a non-retained fraction (NR, 78% of protein) and two retained fractions (R(1) and R(2), 18 and 2.5% of protein, respectively). Both ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Egg triglycerides chromatographed on silicic acid are eluted in a skew curve in which fatty acid composition varies. The triglycerides were cleaved by sodium methoxide in chloroform-methanol at 0 degrees C to yield diglycerides (11.3%) and monoglycerides (17.5% of original triglycerides) after 3 min. Complete cleavage...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-11-01 00:00:00
abstract：:In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic chondrodysplasia punctata, pathological accumulation of phytanic acid results from impaired alpha-oxidation of this branched-chain fatty acid. Previous studies from this laboratory indicated that activation of phytanic acid to its CoA derivative pre...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Inositol lipid kinases have been studied extensively in both plant and animal systems. However, major limitations for in vitro studies of recombinant lipid kinases are the low specific activity and instability of the purified proteins. Our goal was to determine if cyclodextrins would provide an effective substrate del...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D400005-JLR200
更新日期：2004-09-01 00:00:00
abstract：:Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concent...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：:Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Lysophospholipid (LP) research has experienced a period of renaissance with the discovery of the lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) receptors in the late 1990s. Vertebrate LP receptors regulate embryogenesis, vascular development, neurogenesis, uterine development, oocyte survival, immune ce...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800047-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Phospholipase was isolated (in two fractions) from Vipera palestinae venom and it was shown to possess phospholipase A activity (hydrolyzing diacyl-sn-glycerophosphorylcholines, e.g., lecithin, in the 2-position) as well as lysophospholipase (phospholipase B) activity (hydrolyzing 1-monoacyl-sn-glycerophosphorylcholin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-05-01 00:00:00
abstract：:Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, sa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200405-JLR200
更新日期：2003-04-01 00:00:00
abstract：:Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M022673
更新日期：2012-05-01 00:00:00
abstract：:Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-08-01 00:00:00
abstract：:At 123 K, crystals of cholesteryl cis-9-hexadecenoate (cholesteryl palmitoleate, C45H74O2) are monoclinic, space group P2(1) with cell dimensions a = 12.917(7), b = 8.910(5), c = 34.04(1) A, beta = 94.95(7) degrees [lambda(CuK alpha) = 1.5424 A] having two independent molecules (A and B) per unit cell. The crystal str...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has antiatherogenic and antidiabetic effects, but how it confers the atherogenic effects is not well known. To study the antiatherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low density lipoprotein (LDL) to attenuate LDL's atherogenicit...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-21 00:00:00
abstract：:The extent to which cholesterol synthesis is modulated in macrophage foam cells by changes in cholesterol influx and efflux was determined using thioglycollate-elicited peritoneal macrophages from normal and cholesterol-fed White Carneau (WC) and Show Racer (SR) pigeons. In peritoneal macrophages from normocholesterol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The cellular content of total and individual phospholipids and gangliosides was measured in fibroblasts cultured from four normal subjects, three patients with lysosomal lipid storage diseases, and two subjects with homozygous familial hypercholesterolemia. Measurements were made on cells grown in medium containing fe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-03-01 00:00:00
abstract：:Scavenger receptor class B type I (SR-BI) and ABCA1 are structurally dissimilar cell surface proteins that play key roles in HDL metabolism. SR-BI is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterifi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300358-JLR200
更新日期：2004-07-01 00:00:00
abstract：:Incubation of ovarian luteal cells with the bioactive lipid mediator lysophosphatidic acid (LPA) for 180 min abolishes gonadotropin-induced steroid production with no attenuation of the cyclic AMP accumulation. Treatment with the lysolipid also diminishes [14C]steroid production in cells preloaded with either [14C]cho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400423-JLR200
更新日期：2005-05-01 00:00:00
abstract：:Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by ads...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P016816
更新日期：2011-12-01 00:00:00
abstract：:Serum triglyceride (TG) levels are increased in extremely obese individuals, indicating abnormalities in lipid metabolism and insulin resistance. We carried out a genome scan for serum TG in 320 nuclear families segregating extreme obesity and normal weight. Three hundred eighty-two Marshfield microsatellite markers (...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400391-JLR200
更新日期：2005-03-01 00:00:00
abstract：:Recombinant human pancreatic lipase-related protein 2 (rHPLRP2) was produced in the protease A-deficient yeast Pichia pastoris. A major protein with a molecular mass of 50 kDa was purified from the culture medium using SP-Sepharose and Mono Q chromatography. The protein was found to be highly sensitive to the proteoly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600486-JLR200
更新日期：2007-07-01 00:00:00
abstract：:Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2-/- mice contain reduced content of LDs and accumulate less ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M079764
更新日期：2017-11-01 00:00:00
abstract：:Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000648
更新日期：2020-05-01 00:00:00
abstract：:Lymph fistula rats with either biliary fistula or pancreaticobiliary fistula were used to measure coenzyme A-independent mucosal cholesterol esterifying activity in the presence and absence of pancreatic exocrine secretion. Efficiency of pancreatic diversion was verified to minimize contamination of mucosal homogenate...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-01-01 00:00:00
abstract：:In isolated fat cells, the same maximal rate of glycerol production can be induced by epinephrine or ACTH, alone or in combination with each other or with glucagon. With fat cells from rats weighing 150-175 g, the maximal rate of lipolysis attained with glucagon was 75-80% of that produced by epinephrine or ACTH, and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-01-01 00:00:00
abstract：:Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins wer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
