Abstract：
:Lilly PCSK9 antibody LY3015014 (LY) is a monoclonal antibody (mAb) that neutralizes proprotein convertase subtilisin-kexin type 9 (PCSK9). LY decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum. Comparing the epitope of LY with other clinically tested PCSK9 mAbs, it was noted that the LY epitope excludes the furin cleavage site in PCSK9, whereas other mAbs span this site. In vitro exposure of PCSK9 to furin resulted in degradation of PCSK9 bound to LY, whereas cleavage was blocked by other mAbs. These other mAbs caused a significant accumulation of serum PCSK9 and displayed a shorter duration of LDL-cholesterol lowering than LY when administered to mice expressing the WT human PCSK9. In mice expressing a noncleavable variant of human PCSK9, LY behaved like a cleavage-blocking mAb, in that it caused significant PCSK9 accumulation, its duration of LDL lowering was reduced, and its clearance (CL) from serum was accelerated. Thus, LY neutralizes PCSK9 and allows its proteolytic degradation to proceed, which limits PCSK9 accumulation, reduces the CL rate of LY, and extends its duration of action. PCSK9 mAbs with this property are likely to achieve longer durability and require lower doses than mAbs that cause antigen to accumulate.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Schroeder KM,Beyer TP,Hansen RJ,Han B,Pickard RT,Wroblewski VJ,Kowala MC,Eacho PIdoi
10.1194/jlr.M061903subject
Has Abstractpub_date
2015-11-01 00:00:00pages
2124-32issue
11eissn
0022-2275issn
1539-7262pii
jlr.M061903journal_volume
56pub_type
杂志文章abstract：:Using thin-layer chromatography and glass capillary gas-liquid chromatography, we have quantitated the lipids in the germinative, differentiating, and fully cornified layers in human epidermis. As previously noted in nonhuman species, we found progressive depletion of phospholipids coupled with repletion of sterols an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:We present the quantitative and qualitative characteristics of the apolipoprotein (apo) B- and apoA-I-containing lipoprotein subspecies in the plasma of male Golden Syrian hamsters. The spectrum of hamster lipoproteins of d < 1.172 g/ml was subfractionated by isopycnic density gradient ultracentrifugation. ApoB-contai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention due to the limiting concentrations of these lipid amphi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044826
更新日期：2014-02-01 00:00:00
abstract：:Among the family of phospholipases A2 (PLA2s) are the Ca(2+)-independent PLA2s (iPLA2s) and they are designated group VI iPLA2s. In relation to secretory and cytosolic PLA2s, the iPLA2s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA2s or pat...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R058701
更新日期：2015-09-01 00:00:00
abstract：:Some commercial preparations of common natural conjugated bile salts contain impurities (e.g., amines, lipids, and calcium) that are likely to affect their physicochemical properties. A method was developed for purifying commercial preparations of sodium salts of glycine- and taurine-conjugated bile acids. The method ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:The rate-limiting step in the transit of dietary fat across the intestinal absorptive cell is its exit from the endoplasmic reticulum (ER) in a specialized ER-to-Golgi transport vesicle, the prechylomicron transport vesicle (PCTV). PCTV bud off from the ER membranes and have unique features; they are the largest ER-de...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002758
更新日期：2010-05-01 00:00:00
abstract：:The technique of freeze fracture was used to visualize triglyceride (TG) hydrolysis and the production of lipolytic products (LPs) in vitro and in vivo in the presence of bile salts (BS). Three systems were investigated: pure lipolytic products (oleic acid and monoolein) in the presence of a pure bile salt (taurodeoxy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been relat...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R900011-JLR200
更新日期：2009-09-01 00:00:00
abstract：:This paper describes the purification and some of the properties of an enzyme from human spleen that catalyzes the hydrolysis of sphingomyelin with the formation of ceramide and phosphoryl choline. The enzyme, which is located in the subcellular particulate fraction that sediments between 700 and 8500 g, is readily ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-05-01 00:00:00
abstract：:The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300453-JLR200
更新日期：2004-04-01 00:00:00
abstract：:Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyt...
journal_title：Journal of lipid research
pub_type： 杂志文章,随机对照试验
doi：10.1194/jlr.P093013
更新日期：2019-06-01 00:00:00
abstract：:The composition of the emulsified oil and of the micellar phases obtained when a glyceride-fatty acid mixture is dispersed in bile salt solution has been defined. The micellar phase in equilibrium with the emulsified oil phase was obtained by filtration through Millipore filters. The behavior of different lipids in su...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-11-01 00:00:00
abstract：:Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P.,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Fatty acid compositions of glycerophosphatides of developing chick embryonic brain and liver were compared. In brain, ethanolamine and serine glycerophosphatides contained 30-40% polyunsaturated fatty acids, lecithin almost none (except for arachidonic). In the liver, these acids were equally distributed in the phosph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-09-01 00:00:00
abstract：:SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M059709
更新日期：2015-08-01 00:00:00
abstract：:Atherosclerosis is a chronic inflammatory response characterized by the accumulation of cells of innate and acquired immune systems within the intima of the arterial wall. Macrophages are the predominant participant in innate immune responses in atherosclerosis. Protein receptors expressed by macrophages and endotheli...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R400015-JLR200
更新日期：2005-03-01 00:00:00
abstract：:Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies agai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:We have shown previously that low density lipoprotein (LDL) subjected to vortexing forms self-aggregates that are avidly phagocytosed by macrophages. That phagocytic uptake is mediated by the LDL receptor. We now show that LDL self-aggregation is strongly inhibited (80-95%) by the presence of high density lipoprotein ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600248-JLR200
更新日期：2006-11-01 00:00:00
abstract：:Three aliphatic tricarboxylic acids have been found in rat urine. They have been identified as 6-carboxy-5-undecenedioic acid, 6-carboxy-5-dodecenedoic acid, and 6-carboxy-5-tridecenedioic acid. The carbon skeleton structure was determined by mass spectra of the hydrogenated methyl esters. The double bond position was...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into con...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:Cytolipin R, a ceramide tetrahexoside isolated from rat lymphosarcoma, was studied by sequential hydrolysis with specific glycosidases which revealed the anomeric configurations of the glycosidic bonds. Sugar linkages were established by combined gas-liquid chromatography and mass spectrometry of the partially methyla...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-07-01 00:00:00
abstract：:none. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.E046334
更新日期：2013-12-09 00:00:00
abstract：:ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the cu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M012328
更新日期：2011-02-01 00:00:00
abstract：:When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Lec9 Chinese hamster ovary cells were found previously to be defective in the synthesis of N-linked glycans. This appeared to be the result of a defect in the synthesis of oligosaccharide lipid and lipid phosphate (Rosenwald, Stanley, and Krag. 1989. Mol. Cell. Biol. 9: 914-924). In this study we analyzed the steady s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Using a radiometric assay with glycochenodeoxycholic acid as substrate, bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase activity was found in 105,000 g supernatant fractions of liver, proximal intestine, and adrenal gland homogenates from adult hamsters. Optimum conditions for measurement of the hepat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-11-01 00:00:00
abstract：:Sebum is a complex lipid mixture that is synthesized in sebaceous glands and excreted on the skin surface. The purpose of this study was the comprehensive detection of the intact lipids that compose sebum. These lipids exist as a broad range of chemical structures and concentrations. Sebum was collected with SebuTape(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D008391
更新日期：2010-11-01 00:00:00
abstract：:We propose a simple mathematical model to account for the coupling of secretion rates of bile salts, lecithin, and cholesterol into bile. The model assumes that: 1) molecules of "biliary" lecithin and cholesterol enter a functional compartment located in the endoplasmic reticulum of the hepatocyte from which they are ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption consider...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M085043
更新日期：2018-09-01 00:00:00
