Abstract：
:Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity and the regulation of autophagy is cell type specific. Despite adverse consequences of obesity on cardiac structure and function, the contribution of altered cardiac autophagy in response to fatty acid overload is incompletely understood. Here, we report the suppression of autophagosome clearance and the activation of NADPH oxidase (Nox)2 in both high fat-fed murine hearts and palmitate-treated H9C2 cardiomyocytes (CMs). Defective autophagosome clearance is secondary to superoxide-dependent impairment of lysosomal acidification and enzyme activity in palmitate-treated CMs. Inhibition of Nox2 prevented superoxide overproduction, restored lysosome acidification and enzyme activity, and reduced autophagosome accumulation in palmitate-treated CMs. Palmitate-induced Nox2 activation was dependent on the activation of classical protein kinase Cs (PKCs), specifically PKCβII. These findings reveal a novel mechanism linking lipotoxicity with a PKCβ-Nox2-mediated impairment in pH-dependent lysosomal enzyme activity that diminishes autophagic turnover in CMs.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Jaishy B,Zhang Q,Chung HS,Riehle C,Soto J,Jenkins S,Abel P,Cowart LA,Van Eyk JE,Abel EDdoi
10.1194/jlr.M055152subject
Has Abstractpub_date
2015-03-01 00:00:00pages
546-61issue
3eissn
0022-2275issn
1539-7262pii
jlr.M055152journal_volume
56pub_type
杂志文章abstract：:Acyl-CoA:monoglyceride acyltransferase in microsomal preparations from the small intestine of the rat has been measured by means of continuous recording spectrophotometry. The reaction of 5,5'-dithiobis(2-nitrobenzoic acid) with CoA has been employed for this assay and optimal conditions for the reaction have been def...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-07-01 00:00:00
abstract：:Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has been applied primarily to the analysis of glycosphingolipids separated from other complex mixtures by TLC, but it is difficult to obtain quantitative profiling of each glycosphingolipid among the different spots on TLC by MALDI-MS. Thus, the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D800038-JLR200
更新日期：2008-12-01 00:00:00
abstract：:The metabolism of chenodeoxycholic acid by Pseudomonas sp. NCIB 10590 under strict anaerobic conditions was studied. A range of unsaturated acidic and neutral metabolites were isolated and identified. The major acidic product was chola-4,6-dien-3-one-24-oic acid whilst the major neutral product was androsta-4,6-dien-3...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Biosynthetic pathways of phosphatidylcholine and triglyceride were studied in proliferating hepatic endoplasmic reticulum of rats pretreated with phenobarbital. Phosphatidylcholine accounted for the major increment in membrane phospholipid. In vitro measurements of hepatic microsomal enzymes which catalyze phosphatidy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-01-01 00:00:00
abstract：:Bile acids play important roles in the regulation of lipid, glucose, and energy homeostasis. Recent studies suggest that glucose regulates gene transcription in the liver. The aim of this study was to investigate the potential role of glucose in regulation of bile acid synthesis in human hepatocytes. High glucose stim...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002782
更新日期：2010-04-01 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：:Triglyceride (TG) concentration is used as a marker of cardiometabolic risk. However, diurnal and possibly weekday variation exists in TG concentrations. The objective of this work was to investigate weekday variation in TG concentrations among 1.8 million blood samples drawn between 2008 and 2015 from patients in the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M074062
更新日期：2017-06-01 00:00:00
abstract：:In this work, we investigated the impact of testosterone deficiency and cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg) littermates were studied 4 weeks after bilateral orchidectomy or sham operation. Castrate...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600135-JLR200
更新日期：2006-07-01 00:00:00
abstract：:As 5-lipoxygenase (5-LO) is an emerging target in obesity and insulin resistance, we have investigated whether this arachidonate pathway is also implicated in the progression of obesity-related fatty liver disease. Our results show that 5-LO activity and 5-LO-derived product levels are significantly elevated in the li...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800101-JLR200
更新日期：2008-12-01 00:00:00
abstract：:N-acylethanolamines (NAEs) are a group of lipid mediators synthesized in response to a number of physiological and pathological stimuli. Because of the low tissue concentrations of NAEs, analyses often include liquid extraction followed by solid-phase extraction and subsequent quantitation by LC/MS or GC/MS. Reported ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D004606
更新日期：2010-10-01 00:00:00
abstract：:Endothelial dysfunction is a key step in atherosclerosis development. Our recent studies suggested that oxLDL-induced increase in endothelial stiffness plays a major role in dyslipidemia-induced endothelial dysfunction. In this study, we identify oxysterols, as the major component of oxLDL, responsible for the increas...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M027102
更新日期：2012-07-01 00:00:00
abstract：:Human endothelial lipase (EL), a member of the triglyceride lipase gene family, has five potential N-linked glycosylation sites, two of which are conserved in both lipoprotein lipase and hepatic lipase. Reduction in molecular mass of EL after treatment with glycosidases and after treatment of EL-expressing cells with ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400162-JLR200
更新日期：2004-11-01 00:00:00
abstract：:Subcellular localization of nonesterified cholesterol has been determined in normal human fibroblasts from cultures incubated with human low density lipoprotein (LDL). Nonesterified and esterified cholesterol content of fibroblasts, grown initially in the absence of cholesterol, increased significantly after a 1-hour ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Previous studies from our laboratory indicated that pre-germinated brown rice (PR) contained certain unknown bioactive lipids that activated two enzymes related to diabetes: Na+/K+ATPase and homocysteine-thiolactonase. In this paper, we report on the isolation and structural characterization of the activator lipids fr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800257-JLR200
更新日期：2008-10-01 00:00:00
abstract：:Phosphorylcholine-1,2-(14)C and choline-1,2-(14)C-labeled cytidine diphosphate choline are incorporated into lecithin by whole homogenates and particulate fractions of rat retina with optimal incorporation of label by the microsomal fraction. The soluble fraction contains a factor(s) which stimulates incorporation of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-11-01 00:00:00
abstract：:Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate. Insulin-resistant, hypertri...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P068585
更新日期：2016-11-01 00:00:00
abstract：:ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that the transcriptional upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts HDL functio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054742
更新日期：2015-05-01 00:00:00
abstract：:A method is described for determining the long-chain base content of glycosphingolipids after acid hydrolysis, using the new reagent fluorescamine. The reaction is sensitive and can be used to characterize or measure glycosphingolipids in quantities routinely separated by thin-layer chromatography. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-03-01 00:00:00
abstract：:We analyzed Niemann-Pick type C disease 1 (NPC1) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA reve...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200203-jlr200
更新日期：2002-11-01 00:00:00
abstract：:Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M070938
更新日期：2017-02-01 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：:The concentration of cholesterol carried in low density lipoproteins (LDL-C) is primarily determined by the rate at which LDL-C is produced (Jt) and the rate at which the liver takes up this particle through receptor-dependent transport (Jm). The accumulation of specific dietary fatty acids in the liver profoundly alt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 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：:Our previous studies have shown accumulation of GM2 ganglioside during ethanol-induced neurodegeneration in the developing brain, and GM2 elevation has also been reported in other brain injuries and neurodegenerative diseases. Using GM2/GD2 synthase KO mice lacking GM2/GD2 and downstream gangliosides, the current stud...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M056580
更新日期：2015-08-01 00:00:00
abstract：:Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35 rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate 25% of that of parental FAO hepatoma cells, which express high levels of MTP. The inability to express MTP was associated with a complete block in the secreti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：:The sequences of the plasma apolipoproteins have a high degree of internal homology as they contain several 22-mer internal repeats. These amphipathic helical repeats are considered as the structural and functional units of this class of proteins. We proposed that the 22-mer repeats of the plasma apolipoproteins consi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-08-01 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：:Phospholipids serve as central structural components in cellular membranes and as potent mediators in numerous signaling pathways. There are six main classes of naturally occurring phospholipids distinguished by their distinct polar head groups that contain many unique molecular species with distinct fatty acid compos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D051581
更新日期：2014-11-01 00:00:00
abstract：:N-3 trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were isolated from rats fed heated linseed oil. The ability of these acids to inhibit 20:4 n-6 metabolism by human platelets was examined. The concentrations required to inhibit 50% of platelet aggregation (IC50) induced by 2.5 microM 20:4 n-6 were higher for the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
