Abstract：
:Loss of function of Niemann-Pick C1 (NPC1) leads to lysosomal free cholesterol storage, resulting in the neurodegenerative disease Niemann-Pick disease type C (NPC). Significant numbers of patients with NPC also suffer from liver disease. Currently, no treatments exist that alter patient outcome, and it is unknown if recovery from tissue damage can occur even if a treatment were found. Our laboratory developed a strategy to test whether mice can recover from NPC liver disease. We used antisense oligonucleotides to knock down hepatic expression of NPC1 in BALB/C mice for either 9 or 15 weeks. This recapitulated liver disease with hepatomegaly, cell death, and fibrosis. Then, antisense oligonucleotide treatment was halted for an additional 4, 9, or 15 weeks. We report that significant liver recovery occurred even when NPC1 protein expression only partially returned to normal. Several pathological phenotypes were alleviated, including hepatomegaly, cholesterol storage, and liver cell death. Histological examination revealed that foamy cell accumulation was relieved; however, liver fibrosis increased. Additionally, resolution of cholesterol storage and liver cell death took longer in mice with long-term knockdown. Finally, we found that transcription of cholesterol homeostatic genes was significantly disrupted during the recovery phase after long-term knockdown.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Sayre NL,Rimkunas VM,Graham MJ,Crooke RM,Liscum Ldoi
10.1194/jlr.M007211subject
Has Abstractpub_date
2010-08-01 00:00:00pages
2372-83issue
8eissn
0022-2275issn
1539-7262pii
jlr.M007211journal_volume
51pub_type
杂志文章abstract：:The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082362
更新日期：2018-02-01 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed tha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D071068
更新日期：2016-11-01 00:00:00
abstract：:This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormon...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:In contrast to current methods of bile acid analysis that require the separation of bile acids into different groups prior to their analysis, the HPLC method using a reverse phase column and gradient elution that we developed permits the separation and detection of nonconjugated, glycine-conjugated, and esterified bil...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:Scavenger receptor class B type I (SR-BI) has been identified as a functional HDL binding protein that can mediate the selective uptake of cholesteryl ester (CE) from HDL. To quantify the in vivo role of SR-BI in the process of selective uptake, HDL was labeled with cholesteryl ether ([(3)H] CEt-HDL) and (125)I-tyrami...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400191-JLR200
更新日期：2004-11-01 00:00:00
abstract：:The de novo ceramide synthesis pathway is essential to human biology and health, but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; converse...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P094433
更新日期：2019-09-01 00:00:00
abstract：:The alpha-naphthylisothiocyanate (ANIT)-treated rat was evaluated as a model for lipoprotein metabolism in cholestatic liver disease. Alterations in lipoprotein composition over a period of 120 h after ANIT treatment (100 mg/kg) were studied. Eighteen hours after treatment, plasma bilirubin and bile acid levels began ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:The enzymic incorporation of choline-1,2-(14)C from CDP-choline-1,2-(14)C into phosphatidylcholine by spinach leaf preparations was characterized. The enzyme catalyzing the incorporation, choline phosphotransferase, had a pH optimum of about 8.0 and required either Mn(2+) or Mg(2+) as cofactor. The saturation concentr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-07-01 00:00:00
abstract：:We have previously shown that expression of a human apoE cDNA in J774 macrophages enhances cholesterol efflux to HDL3. We have also shown that endogenous apoE expression produces a cell surface pool of apoE associated with proteoglycans. In this series of experiments, we first demonstrate the presence of a cell surfac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:Cerebrotendinous xanthomatosis (CTX) is a rare, recessively inherited lipid storage disease characterized by a markedly reduced production of chenodeoxycholic acid and an increased formation of 25-hydroxylated bile alcohols and cholestanol. Patients with this disease are known to have mutations in the sterol 27-hydrox...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:In mammals, white adipose tissue (WAT) stores and releases lipids, whereas brown adipose tissue (BAT) oxidizes lipids to fuel thermogenesis. In obese individuals, WAT undergoes profound changes; it expands, becomes dysfunctional, and develops a low-grade inflammatory state. Importantly, BAT content and activity declin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M079665
更新日期：2018-05-01 00:00:00
abstract：:Plasma phospholipid transfer protein (PLTP) interacts with HDL particles and facilitates the transfer of phospholipids from triglyceride (TG)-rich lipoproteins to HDL. Overexpressing human PLTP in mice increases the susceptibility to atherosclerosis. In human plasma, high-active and low-active forms of PLTP exist. To ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800080-JLR200
更新日期：2008-12-01 00:00:00
abstract：:The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by nor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:Rhizobium chitolipooligosaccharides (CLOSs) are heterogeneous fatty acylated N-acetyl glucosamine oligomers with variations in both the polar (hydrophilic) oligosaccharide head group and the non-polar (hydrophobic) fatty acyl chain. They trigger root hair deformation and cortical cell divisions in legume roots during ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:We have developed the technique of rapid (< 2 h) centrifugal ultrafiltration to measure the inter-mixed micellar/vesicular (non-lecithin-associated) bile salt (BS) concentrations (IMC) of individual BS in model biles. This methodology uses a centrifugal concentrator with a reinforced membrane, through which a small fr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 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：:Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contain...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M003657
更新日期：2010-08-01 00:00:00
abstract：:Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-diHETE and 5,11-diHETE in isolated human leuk...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M017822
更新日期：2012-01-01 00:00:00
abstract：:The palmitate (PA) binding and transport capacity of human and bovine red cell membranes enables us to establish, in a biological system, the existence of a well-defined monomer concentration in equilibrium with PA bound to bovine serum albumin (BSA, 30 microM) inside the resealed red cell ghosts. Supernatants of susp...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is the rate-controlling enzyme of cholesterol synthesis, and owing to its biological and pharmacological relevance, researchers have investigated several compounds capable of modulating its activity with the hope of developing new hypocholesterolemic drugs. In particular,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M011817
更新日期：2011-05-01 00:00:00
abstract：:Two assays for the quantitative measurement of HMG-CoA reductase, the major regulatory enzyme in hepatic cholesterol biosynthesis, are described. The first of these procedures employs thin-layer chromatography (TLC) of the reaction product on plastic-backed silica gel G strips impregnated with ammonium carbonate. The ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:A subgroup of peroxisomal disorders, peroxisome biogenesis defects (PBD), can be differentiated by elevated levels of C(27) bile acids in plasma and bile. Patients with peroxisomal disorders, who lack the ability to chain-shorten the C(27) bile acid intermediates into C(24) bile acids, show elevated levels of C(27) bi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs throug...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089714
更新日期：2019-04-01 00:00:00
abstract：:Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1194/jlr.P800061-JLR200
更新日期：2009-07-01 00:00:00
abstract：:The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of 3H2O and [14C]mevalonate into digitonin-precipitable sterols with time of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-08-01 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：:A multiplexed assay was developed by MS to analyze, in a single run, six major human Apos involved in lipoprotein metabolism: ApoA-I, ApoA-II, ApoB100, ApoC-II, ApoC-III, and ApoE. This method was validated in vivo in six subjects who received a 14 h constant infusion of [5,5,5-(2)H3]L-leucine at 10 μM/kg/h. Plasma li...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D064618
更新日期：2016-03-01 00:00:00
abstract：:Significant amounts of ursodeoxycholic acid (UDCA) used for the treatment of patients with primary biliary cirrhosis (PBC) become epimerized at C-3 to isoUDCA. We investigated the metabolism of isoUDCA and a possible pharmacologic effect in five patients (51.4 +/- 5.8 years old; 3 females, 2 males) with PBC and persis...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Due to conflicting reports concerning the relationship between phospholipid transfer protein (PLTP) activity and mass in plasma, the protein concentration and activity of PLTP were assessed in fractions isolated by fast protein liquid chromatography from the plasma of healthy normolipidemic individuals. Using both pol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-02-01 00:00:00
