Abstract：
:Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals. First, with normal male Wistar rats, the levels of GGA in liver were found to be far greater than those in other organs analyzed. Second, we demonstrated the metabolic GGA labeling from the 13C-labeled mevalonolactone in the human hepatoma-derived cell line, HuH-7. Isotopomer spectral analysis revealed that approximately 80% of the cellular GGA was newly synthesized from mevalonate (MVA) in 12 h and the acid picked up preexisting farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP), suggesting that GGA is derived from FPP and GGPP through the MVA pathway. Third, zaragozic acid A, a squalene synthase inhibitor, induced dose-dependent upregulation of endogenous GGA content in HuH-7 cells and their concomitant cell death. These results strongly suggest that a cancer-preventive GGA is biosynthesized via the MVA pathway in mammals.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Shidoji Y,Tabata Ydoi
10.1194/jlr.M090548subject
Has Abstractpub_date
2019-03-01 00:00:00pages
579-593issue
3eissn
0022-2275issn
1539-7262pii
jlr.M090548journal_volume
60pub_type
杂志文章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：:Bovine aortic endothelial cells take up 12-hydroxyeicosatetraenoic acid (12-HETE), a lipoxygenase product formed from arachidonic acid. The uptake of [3H]12-HETE reached a maximum in 2 to 4 h. At this time, from 75 to 80% of the incorporated radioactivity was contained in phospholipids, about 85% of the esterified rad...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia. The aim of the present study was id...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400062-JLR200
更新日期：2004-06-01 00:00:00
abstract：:Unesterified cholesterol is an essential structural component of the plasma membrane of every cell. During evolution, this membrane came to play an additional, highly specialized role in the central nervous system (CNS) as the major architectural component of compact myelin. As a consequence, in the human the mean con...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R400004-JLR200
更新日期：2004-08-01 00:00:00
abstract：:Adipocyte triglyceride storage provides a reservoir of energy that allows the organism to survive times of nutrient scarcity, but excessive adiposity has emerged as a health problem in many areas of the world. Monoacylglycerol acyltransferase (MGAT) acylates monoacylglycerol to produce diacylglycerol; the penultimate ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M084947
更新日期：2018-09-01 00:00:00
abstract：:De novo synthesis and turnover of endogenous ceramide in cultured skin fibroblasts from patients affected with Farber lipogranulomatosis were studied by biosynthetical labeling of cellular sphingolipids with [14C]serine. The cellular uptake of [14C]serine and incorporation into de novo synthesized ceramide was similar...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:For the last 30 years fibrates have been widely prescribed to treat human dyslipidemia. However, the primary mechanism by which they lower plasma lipid levels is still unknown. Studies with transgenic mice have suggested that changes in apoC-III expression levels have a dramatic influence on plasma triglyceride levels...
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 transcriptional regulation of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) by hormones and signal transduction pathways was studied by transient transfection assay of the promoter activity. HepG2 cells were transfected with deletion mutants of the CYP7 upstream region linked to the luciferase reporter gene....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Different types of dietary fat were administered [saturated fat (SE), corn oil (CE) and fish oil (FE)] with ethanol to induce varying severities of liver ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:14C-labeled oleic acid and (3)H-labeled monoether in a bile salt solution were perfused through three types of plastic tubing. Large proportions of lipid were lost to the walls of silicone rubber and polyvinyl chloride tubes. The major portion of the lipid lost was recoverable only when chloroform-methanol was perfuse...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-09-01 00:00:00
abstract：:Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understoo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M083899
更新日期：2018-08-01 00:00:00
abstract：:Rats were fed a low protein diet deficient in and supplemented with lysine and threonine. Liver lipids contained more lecithin, sphingomyelin, and free fatty acids, and less amino phospholipids in the deficient rats. No variations in fatty acid composition of choline- and ethanolamine-containing phospholipids were fou...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-07-01 00:00:00
abstract：:Previous findings with various murine tumor cell lines suggest an association between ganglioside GM3 and cell cohesive properties. The influence of GM3 on cohesion was studied in two mouse brain tumor cell lines: ependymoblastoma (EPEN) and CT-2A. In culture, the EPEN cells grow as islands and contain GM3 as the only...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:Of the six fatty acid elongase (Elovl) subtypes expressed in mammals, adult rat liver expresses four subtypes: Elovl-5 > Elovl-1 = Elovl-2 = Elovl-6. Overnight starvation and fish oil-enriched diets repressed hepatic elongase activity in livers of adult male rats. Diet-induced changes in elongase activity correlate wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400335-JLR200
更新日期：2005-04-01 00:00:00
abstract：:MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033779
更新日期：2013-09-01 00:00:00
abstract：:The Delta6-desaturase catalyzes key steps in long-chain polyunsaturated fatty acid biosynthesis. Although the gene coding for this enzyme has been isolated in diverse animal species, the protein structure remains poorly characterized. In this work, rat Delta6-desaturase expressed in COS-7 cells was shown to localize i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300339-JLR200
更新日期：2004-01-01 00:00:00
abstract：:Reversed phase high pressure liquid chromatography (HPLC) solvent systems have been developed for the separation of intermediates in the formation of bile acids and bile acid conjugates from cholesterol. Four different mobile phases (water-methanol, 10 mM acetate buffer (pH 4.37)-methanol, 30 mM trifluoroacetic acid (...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
abstract：:Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a fatty acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation of long-chain fatty acids. Our previous in vitro studies suggested that ELOVL6 elongated long-chain saturated fatty acids an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054353
更新日期：2014-12-01 00:00:00
abstract：:ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400450-JLR200
更新日期：2005-09-01 00:00:00
abstract：:Small angle X-ray diffraction was used to examine arterial smooth muscle cell (SMC) plasma membranes isolated from control and cholesterol-fed (2%) atherosclerotic rabbits. A microsomal membrane enriched with plasma membrane obtained from animals fed cholesterol for up to 13 weeks showed a progressive elevation in the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:The behavior of human omental fat cells in vitro has been examined in order to define conditions under which glucose is converted to glyceride-glycerol and glyceride fatty acids. Synthesis of glyceride fatty acids from glucose reached maximal rates only after several hours of incubation in Krebs-Henseleit bicarbonate ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-05-01 00:00:00
abstract：:Evidence is given that the heart of the cardiomyopathic UM-X7.1 hamster has a lipid composition different from that of the same tissue isolated from animals of the Syrian hamster parent strain. Also, noncardiac tissues from cardiomyopathic and healthy hamsters exhibit significant compositional differences. On the basi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is several times higher than expected from the sn-2 acyl composition of plasma phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much lower than expected. To explain these discrepancies, we proposed that LCAT transfe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400197-JLR200
更新日期：2004-12-01 00:00:00
abstract：:The common bile acids of rat bile (chenodeoxycholic, hyodeoxycholic, cholic, alpha-muricholic, and beta-muricholic acids) are completely separated by a new thin-layer chromatographic system. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-05-01 00:00:00
abstract：:Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Delta-6 desaturase (D6D) catalyzes the first step in the synthesis of highly unsaturated fatty acids (HUFA) such as arachidonic (AA), docosapentaenoic (DPAn-6), and docosahexaenoic (DHA) acids, as well as the last desaturation of DPAn-6 and DHA. We created D6D-null mice (-/-), which enabled us to study HUFA deficiency...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M900039-JLR200
更新日期：2009-09-01 00:00:00
abstract：:Baboons possess Lp[a] that is similar to human Lp[a], including the presence of the unique protein, apo[a]. Baboon apo[a] occurred in at least nine isoforms distinguishable by size. Isoforms were resolved by 3-12% polyacrylamide gradient gel electrophoretic separation of serum proteins, and were detected with baboon a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary and intestinal removal of neutral sterols. Here, we identify a binding site for the orphan nuclear receptor liver receptor homolog-1 (LRH-1) at nt 134-142 of the ABCG5/ABCG8 intergenic region necessary for the activity of both the ABCG...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.C400002-JLR200
更新日期：2004-07-01 00:00:00
abstract：:We investigated the formation and pharmacology of prostaglandin E(3) (PGE(3)) derived from fish oil eicosapentaenoic acid (EPA) in human lung cancer A549 cells. Exposure of A549 cells to EPA resulted in the rapid formation and export of PGE(3.) The extracellular ratio of PGE(3) to PGE(2) increased from 0.08 in control...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300455-JLR200
更新日期：2004-06-01 00:00:00
