Apolipoprotein Gene Expression Research Articles

Regulation of apolipoprotein gene expression and plasma high-density lipoprotein composition in experimental nephrosis

Hepatic and intestinal RNA levels were measured in rats made nephrotic by injection of puromycin aminonucleoside (PAN). The following increases in hepatic RNA levels, relative to controls, were measured: poly A + (1.2), ribosomal (1.2), mRNA levels for transferrin (1.8), albumin (3.8) apolipoprotein (apo)E (2.3), apoB (2.5), apoA-II (1.9) and apoA-I (6.1). Increases of 1.5- to 2.2-fold in hepatic mRNA levels for albumin, apoA-II, apoB and apoE were measured in pre-nephrotic animals killed before the onset of proteinuria. Intestinal RNA levels in pre-nephrotic and nephrotic animals were not significantly different from control values. Transcription of the hepatic apoA-I gene increased 1.8-fold in nephrotic animals compared to controls. Immunological detection of apolipoproteins in high-density lipoproteins (HDL) separated by gradient gel elecrrophoresis indicated an increase in apoA-I and a decrease in apoA-IV and apoE containing HDL particles in nephrosis. To simulate the effects of increased apoA-I gene expression, human apoA-I was added to rat plasma in vivo and in vitro. ApoE was displaced from HDL by increased concentration of apoA-I. The results indicate that relatively small changes in apoA-I levels in the serum lead to significant changes in the apolipoprotein composition of HDL.

Apolipoprotein gene expression in the rat is regulated in a tissue-specific manner by thyroid hormone

We have studied the regulation of rat intestinal and hepatic apolipoprotein gene expression, in vivo, after alterations in thyroid hormone status. When compared to those of chow-fed controls, rates of synthesis of intestinal apoA-I and apoB-48 decreased 60-66% in hypothyroid animals and increased three- to fourfold after triiodothyronine (T3) administration. These changes were not accompanied by changes in mRNA abundance. By contrast, intestinal apoA-IV synthesis rates and mRNA abundance were both unaltered over the range of thyroid hormone manipulations tested. Hepatic apoA-I and apoA-IV synthesis rates decreased by 70-80% in hypothyroid animals, while synthesis rates and mRNA abundance increased coordinately six- to eightfold when hypothyroid rats were made hyperthyroid. Hepatic apoE synthesis rates increased twofold in hypothyroid rats and decreased sevenfold in hyperthyroid animals. ApoE mRNA abundance, however, was comparable in all groups. Hypothyroid animals had reduced synthesis rates of hepatic apoB-100 and apoB-48. After induction of hyperthyroidism, apoB-100 synthesis (studied from 5 to 60 min) was undetectable (less than 0.01%) without further change in apoB-48 synthesis and without alterations in either apoB mRNA abundance or transcript size. Despite undetectable hepatic apoB-100 synthesis rates in hyperthyroid animals, total plasma triglyceride secretion rates (after Triton WR-1339 injection) were normalized compared to a 50% decrease in hypothyroid rats. Taken together, the data provide evidence for tissue-specific, independent regulation of apolipoprotein gene expression in vivo. Furthermore, the data suggest that aspects of hepatic triglyceride assembly and secretion and apolipoprotein gene expression may be coordinately responsive to alterations in thyroid hormone status.

Apolipoprotein gene expression in the rabbit: abundance, size, and distribution of apolipoprotein mRNA species in different tissues

We have used human apolipoprotein cDNAs as hybridization probes to study the relative abundance and distribution of apolipoprotein mRNAs in rabbit tissues by RNA blotting analysis. The tissues surveyed included liver, intestine, lung, pancreas, spleen, stomach, skeletal muscle, testis, heart, kidney, adrenal, aorta, and brain. We found that liver is the sole or major site of synthesis of apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, and apoE, and the intestine is a major site of synthesis of apoA-I, apoA-IV, and apoB. Minor sites of apolipoprotein mRNA synthesis were as follows: apoA-I, liver and skeletal muscle; apoA-IV, spleen and lung; apoB, kidney; apoC-II and apoC-III, intestine. ApoE mRNA was detected in all tissues surveyed with the exception of skeletal muscle. Sites with moderate apoE mRNA (10% of the liver value) were lung, brain, spleen, stomach, and testis. All rabbit mRNAs had forms with sizes comparable to their human counterparts. In addition, hybridization of hepatic and intestinal RNA with human apoA-IV and apoB probes produced a second hybridization band of approximately 2.4 and 8 kb, respectively. Similarly, hybridization of rabbit intestinal RNA with human apoC-II produced a hybridization band of 1.8 kb. The 8 kb apoB mRNA form may correspond to the apoB-48 mRNA, whereas the apoA-IV- and apoC-II-related mRNA species have not been described previously. This study provides a comprehensive survey of the sites of apolipoprotein gene expression and shows numerous differences in both the abundance and the tissue distribution of several apolipoprotein mRNAs between rabbit and human tissues. These findings and the observation of potentially new apolipoprotein mRNA species are important for our understanding of the cis and trans acting factors that confer tissue specificity as well as factors that regulate the expression of apolipoprotein genes in different mammalian species.

Expression of the Human Serum Apolipoprotein AI and AII Genes inXenopus laevisOocytes. Lipid-Associated Secretion of Gene Products

The two major apolipoproteins of plasma high-density lipoproteins (HDL) are apolipoprotein AI (apo AI) and AII (apo AII). The apo AI and the correctly oriented apo CIII genes separated by 2.6 kb were obtained by fusion of two human lambda-genomic clones. The apo AII gene was isolated as a 3 kb clone. These apolipoprotein genes have been injected independently and together into Xenopus laevis oocytes and their expression studied. Both apolipoprotein genes were transcribed and translated into their preproforms and processed in Xenopus laevis oocytes to their proforms. They were secreted into the medium associated with newly synthesized phospholipids and neutral lipids as particles floating in the high-density lipoprotein range between 1.12 and 1.21 g/ml. Secreted apo AI is associated mainly with newly synthesized phosphatidylethanolamine and little triglyceride, apo AII with phosphatidylethanolamine, lysophosphatidylethanolamine and neutral lipids. Simultaneous injection of the apo AI and apo AII genes led to the secretion of both apoproteins which separated into two bands during CsCl-density gradient centrifugation. The heavier particles were associated with proapo AI and AII, phosphatidylethanolamine (greater than 90%) and traces of lysophosphatidylethanolamine as lipid components. Proapo AII was immunoprecipitated from the less dense fraction and found to be mainly associated with lysophosphatidylethanolamine. Radiolabelled newly synthesized apolipoproteins in secreted particles were characterized by immunoprecipitation after delipidation of the secreted lipoprotein particles. The oocyte-system proved very suitable for studies of the expression of serum apolipoprotein genes, the assembly of the apolipoproteins with specific lipids to lipoprotein particles and their secretion.

41] Characterization of the apolipoprotein A-I—C-III gene complex

Publisher Summary The human apolipoprotein A-I (apoA-I) and apolipoprotein C-III (apoC-III) genes have been isolated and shown that they are physically linked. This chapter describes the methodology employed to carry out structural comparisons of this gene complex between normal individuals and patients with combined apoA-I-apoC-III deficiency and premature atherosclerosis that indicates the presence of a DNA insertion in the coding regions of the apoA-I gene of these patients. The preliminary observations have indicated that this DNA insertion is the result of a DNA rearrangement in the apoAI-apoC-III gene locus of these patients and that this rearrangement has also interfered with apoC-III gene expression. Thus, comparison of apolipoprotein gene structures in normal and diseased states can reveal mutations affecting gene expression, which may be directly related to the development of the disease. The chapter suggests that in future, it will be interesting to compare possible differences in factors controlling apolipoprotein gene expression in normal and diseased states.

Effects of high-carbohydrate diets on lipid and carbohydrate metabolism in the rat.

ARTICLESEffects of high-carbohydrate diets on lipid and carbohydrate metabolism in the ratRP Eaton, and DM KipnisRP Eaton, and DM KipnisPublished Online:01 Oct 1969https://doi.org/10.1152/ajplegacy.1969.217.4.1160MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByMolecular aspects of fructose metabolism and metabolic diseaseCell Metabolism, Vol. 33, No. 12A 72-hour high fat diet increases transcript levels of the neuropeptide galanin in the dorsal hippocampus of the rat11 August 2015 | BMC Neuroscience, Vol. 16, No. 1Modulation of insulin secretion by feeding behavior and physical activity: Possible beneficial effects on obese and aged ratsNeuroscience & Biobehavioral Reviews, Vol. 20, No. 2Effect of troglitazone (CS-045) and bezafibrate on glucose tolerance, Liver Glycogen synthase activity, and β-oxidation in fructose-fed ratsMetabolism, Vol. 44, No. 12Effect of sucrose diet on expression of apolipoprotein genes A-I, C-III and A-IV in rat liverAtherosclerosis, Vol. 95, No. 2-3Insulin secretion to glucose stimulus in pancreatic islets isolated from rats fed unbalanced dietsPhysiology & Behavior, Vol. 50, No. 4Effect of Sucrose Diet on Apolipoprotein Biosynthesis in Rat LiverJournal of Biological Chemistry, Vol. 264, No. 2Health AspectsEffect of high sucrose diet on insulin secretion and insulin action: a study in the normal ratDiabetologia, Vol. 30, No. 4Effect of diet on glucose tolerance and insulin response in chemically diabetic ratsMetabolism, Vol. 31, No. 12Studies of the mechanism of fructose-induced hypertriglyceridemia in the ratMetabolism, Vol. 31, No. 11Hyperinsulinemia in fructose-induced hypertriglyceridemia in the ratMetabolism, Vol. 29, No. 4Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats.Journal of Lipid Research, Vol. 20, No. 3Influence of fructose feeding on individual enzymic reactions in the formation and metabolism of bile acids in rat liver homogenates10 January 2017 | British Journal of Nutrition, Vol. 36, No. 2Effect of qualitatively different carbohydrates on lipoprotein spectrum and composition of blood lipidsBulletin of Experimental Biology and Medicine, Vol. 81, No. 4Alterations in levels and interrelations of plasma apolipoproteins induced by dietMetabolism, Vol. 25, No. 3Mammalian Low Density LipoproteinsLipoproteins in AnimalsDrugs, lipids and atherosclerosisPharmacological Research Communications, Vol. 7, No. 2DECREASED GLUCAGON ACTIVITY: A MECHANISM FOR GENETIC AND ACQUIRED ENDOGENOUS HYPERLIPÆMIAThe Lancet, Vol. 304, No. 7896Kohlehydrat- und Palmitinsäurestoffwechsel am Myokard der Ratte bei HypoxieBasic Research in Cardiology, Vol. 68, No. 3Hypolipemic action of glucagon in experimental endogenous lipemia in the ratJournal of Lipid Research, Vol. 14, No. 3Plasma pre-α-lipoproteins in ethionine induced fatty liver in ratsExperientia, Vol. 29, No. 4Effects of high sucrose diets and 4-aminopyrazolopyrimidine on serum lipids and lipoproteins in the ratJournal of Lipid Research, Vol. 12, No. 5Utilization of exogenous free fatty acids for the production of very low density lipoprotein triglyceride by livers of carbohydrate-fed ratsJournal of Lipid Research, Vol. 12, No. 5The effect of prolonged fasting and of glucose refeeding on rat serum and liver lipid levelsLipids, Vol. 6, No. 5Intermediary Aspects and Tissue Interactions of Ruminant Fat MetabolismJournal of Dairy Science, Vol. 54, No. 4Co-induction of the hepatic amino acid transport system and tyrosine aminotransferase by theophylline, glucagon and dibutyryl-cyclic AMPLife Sciences, Vol. 9, No. 19Synthesis of Phospholipids and Triglycerides in Human Liver Slices8 July 2009 | Scandinavian Journal of Clinical and Laboratory Investigation, Vol. 26, No. 4 More from this issue > Volume 217Issue 4October 1969Pages 1160-1168 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.217.4.1160PubMed5824318History Published online 1 October 1969 Published in print 1 October 1969 Metrics