scholarly journals Transfer of exogenous cholesterol to microsomes of hepatocytes investigated with [3H]desmosterol tracer

1983 ◽  
Vol 216 (1) ◽  
pp. 137-142 ◽  
Author(s):  
E H Goh
Keyword(s):  
Mass Transfer ◽  
Endoplasmic Reticulum ◽  
Bile Acids ◽  
Plasma Cholesterol ◽  
Physiological Functions ◽  
Steryl Esters ◽  
Exogenous Cholesterol ◽  
Uptake And Metabolism ◽  
Metabolic Tracer

The feasibility of using exogenous [3H]desmosterol as a mass metabolic tracer for exogenous non-esterified cholesterol in hepatocytes is investigated with albumin-bound non-esterified cholesterol containing [3H]desmosterol and [14C] cholesterol tracers. The amounts of uptake and metabolism of exogenous cholesterol monitored by either tracer are the same. In addition, the conversion of [3H]desmosterol into [3H]cholesterol by the delta 24-sterol reductase in the microsomes can be used as an estimate for the mass transfer of exogenous cholesterol to the microsomes. The results obtained indicate that only a small fraction of exogenous cholesterol that was transferred to the microsomes was metabolized into bile acids and steryl esters. The technique of estimating the mass transfer of exogenous cholesterol to the microsomes with [3H]desmosterol may be of importance in investigations dealing with the effect of exogenous plasma cholesterol on changes in the physiological functions of the endoplasmic reticulum in the cells.

scholarly journals Release of calcium from the endoplasmic reticulum by bile acids in rat liver cells.

1988 ◽  
Vol 263 (5) ◽  
pp. 2299-2303 ◽  
Author(s):  
L Combettes ◽  
M Dumont ◽  
B Berthon ◽  
S Erlinger ◽  
M Claret
Keyword(s):  
Endoplasmic Reticulum ◽  
Bile Acids ◽  
Rat Liver ◽  
Liver Cells ◽  
Rat Liver Cells

Bile Acids: The Good, the Bad, and the Ugly

Physiology ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Alan F. Hofmann
Keyword(s):  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Absorption ◽  
Bile Acid Metabolism ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor

Bile acids, amphipathic end products of cholesterol metabolism, are “good” in the infant because they enhance lipid absorption and thereby promote growth. Bile acids also induce bile flow and biliary lipid secretion. The enterohepatic circulation of bile acids is “bad” in the adult because it downregulates hepatocyte low-density lipoprotein receptor activity and thereby elevates plasma cholesterol levels. Defects in bile acid metabolism such as impaired biosynthesis or transport are “ugly” because they cause morbidity and death. New approaches for treating these defects are being developed.

scholarly journals Physiological importance of NGLY1, as revealed by rodent model analyses

2021 ◽  
Author(s):  
Haruhiko Fujihira ◽  
Makoto Asahina ◽  
Tadashi Suzuki
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Control System ◽  
Animal Models ◽  
Rodent Model ◽  
Rodent Models ◽  
Future Perspectives ◽  
Physiological Functions ◽  
Physiological Importance ◽  
Glycan Degradation

Summary Cytosolic peptide:N-glycanase (NGLY1) is an enzyme that cleaves N-glycans from glycoproteins that has been retrotranslocated from the endoplasmic reticulum (ER) lumen into the cytosol. It is known that NGLY1 is involved in the degradation of cytosolic glycans (non-lysosomal glycan degradation) as well as ER-associated degradation (ERAD), a quality control system for newly synthesized glycoproteins. The discovery of NGLY1 deficiency, which is caused by mutations in the human NGLY1 gene and results in multisystemic symptoms, has attracted interest in the physiological functions of NGLY1 in mammals. Studies using various animal models led to the identification of possible factors that contribute to the pathogenesis of NGLY1 deficiency. In this review, we summarize phenotypic consequences that have been reported for various Ngly1-deficient rodent models, and discuss future perspectives to provide more insights into the physiological functions of NGLY1.

Bile secretion during experimental hyperthyroidism in the dog

1960 ◽  
Vol 199 (5) ◽  
pp. 893-897 ◽  
Author(s):  
Joseph H. Gans
Keyword(s):  
Bile Acids ◽  
Plasma Cholesterol ◽  
Bile Secretion ◽  
The State ◽  
Biliary Cholesterol ◽  
Thyroid Activity ◽  
Experimental Hyperthyroidism ◽  
Significant Change

Experimental hyperthyroidism in the dog was accompanied by a significant decrease in the enterohepatic content of bile acids with no significant change in biliary cholesterol output. Plasma cholesterol concentrations decreased consistently in all hyperthyroid dogs. Alterations in the diet were followed by marked changes in bile secretion both in the euthyroid and hyperthyroid dogs. The euthyroid dogs given a diet supplemented with protein and cholesterol secreted greater amounts of cholesterol and bile acids into bile. Hyperthyroidism, induced in dogs given the supplemented diet, was associated with a decrease in the biliary output of both cholesterol and bile acids when compared with the controls given the supplemented unchanged. Changes in the secretion of biliary steroids and sterols during experimental hyperthyroidism in the dog may be the result of a disproportionate increase in the rate of the oxidation of acetate. Confirming earlier investigations in thyroidectomized dogs, dietary constituents may influence plasma cholesterol concentrations in the dog regardless of the state of thyroid activity.

High plasma cholesterol in drug-induced cholestasis is associated with enhanced hepatic cholesterol synthesis

1999 ◽  
Vol 276 (5) ◽  
pp. G1165-G1173 ◽  
Author(s):  
Jeffrey W. Chisholm ◽  
Patrick Nation ◽  
Peter J. Dolphin ◽  
Luis B. Agellon
Keyword(s):  
Bile Acids ◽  
Cholesterol Synthesis ◽  
Cell Membranes ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Hepatic Cell ◽  
Plasma Lipoproteins ◽  
Liver Cholesterol ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis

In α-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7α-hydroxylase activity was decreased by ∼70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma.

scholarly journals Dietary Cocoa Powder Improves Hyperlipidemia and Reduces Atherosclerosis in apoE Deficient Mice through the Inhibition of Hepatic Endoplasmic Reticulum Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hua Guan ◽  
Yan Lin ◽  
Liang Bai ◽  
Yingfeng An ◽  
Jianan Shang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Molecular Mechanisms ◽  
Plasma Cholesterol ◽  
Group Analysis ◽  
Pcr Analysis ◽  
Control Group ◽  
Cocoa Powder ◽  
Beneficial Effects ◽  
Apoe Knockout Mice

Cocoa powder is rich in flavonoids, which have many beneficial effects on human health, including antioxidative and anti-inflammatory effects. The aim of our study was to investigate whether the intake of cocoa powder has any influence on hyperlipidemia and atherosclerosis and examine the underlying molecular mechanisms. We fed apoE knockout mice a Western diet supplemented with either 0.2% (low group) or 2% (high group) cocoa powder for 12 weeks. The groups fed dietary cocoa powder showed a significant reduction in both plasma cholesterol levels and aortic atherosclerosis compared to the control group. Analysis of mRNA profiling of aortic atherosclerotic lesions revealed that the expression of several genes related to apoptosis, lipid metabolism, and inflammation was significantly reduced, while the antiapoptotic gene Bcl2 was significantly increased in the cocoa powder group compared to the control. RT-PCR analysis along with Western blotting revealed that a diet containing cocoa powder inhibited the expression of hepatic endoplasmic reticulum stress. These data suggest that cocoa powder intake improves hyperlipidemia and atherosclerosis, and such beneficial effects are possibly mediated through the suppression of hepatic endoplasmic reticulum stress.

scholarly journals OATP1B3-1B7, a novel organic anion transporting polypeptide, is modulated by FXR ligands and transports bile acids

2019 ◽  
Vol 317 (6) ◽  
pp. G751-G762 ◽  
Author(s):  
Vanessa Malagnino ◽  
Janine Hussner ◽  
Ali Issa ◽  
Angela Midzic ◽  
Henriette E. Meyer zu Schwabedissen
Keyword(s):  
Endoplasmic Reticulum ◽  
Bile Acid ◽  
Bile Acids ◽  
Smooth Endoplasmic Reticulum ◽  
Organic Anion ◽  
Farnesoid X Receptor ◽  
Organic Anion Transporter ◽  
Organic Anion Transporting Polypeptide ◽  
Anion Transporter ◽  
Solute Carrier

Organic anion transporting polypeptide (OATP) 1B3–1B7 (LST-3TM12) is a member of the OATP1B [solute carrier organic anion transporter ( SLCO) 1B] family. This transporter is not only functional but also expressed in the membrane of the smooth endoplasmic reticulum of hepatocytes and enterocytes. OATP1B3–1B7 is a splice variant of SLCO1B3 in which the initial part is encoded by SLCO1B3, whereas the rest of the mRNA originates from the gene locus of SLCO1B7. In this study, we not only showed that SLCO1B3 and the mRNA encoding for OATP1B3–1B7 share the 5′ untranslated region but also that silencing of an initial SLCO1B3 exon lowered the amount of SLCO1B3 and of SLCO1B7 mRNA in Huh-7 cells. To validate the assumption that both transcripts are regulated by the same promoter we tested the influence of the bile acid sensor farnesoid X receptor (FXR) on their transcription. Treatment of Huh-7 and HepaRG cells with activators of this known regulator of OATP1B3 not only increased SLCO1B3 but also OATP1B3–1B7 mRNA transcription. Applying a heterologous expression system, we showed that several bile acids interact with OATP1B3–1B7 and that taurocholic acid and lithocholic acid are OATP1B3–1B7 substrates. As OATP1B3–1B7 is located in the smooth endoplasmic reticulum, it may grant access to metabolizing enzymes. In accordance are our findings showing that the OATP1B3–1B7 inhibitor bromsulphthalein significantly reduced uptake of bile acids into human liver microsomes. Taken together, we report that OATP1B3–1B7 transcription can be modulated with FXR agonists and antagonists and that OATP1B3–1B7 transports bile acids. NEW & NOTEWORTHY Our study on the transcriptional regulation of the novel organic anion transporting polypeptide (OATP) 1B3–1B7 concludes that the promoter of solute carrier organic anion transporter ( SLCO) 1B3 governs SLCO1B3–1B7 transcription. Moreover, the transcription of OATP1B3–1B7 can be modulated by farnesoid X receptor (FXR) agonists and antagonists. FXR is a major regulator in bile acid homeostasis that links OATP1B3–1B7 to this physiological function. Findings in transport studies with OATP1B3–1B7 suggest that this transporter interacts with the herein tested bile acids.

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