scholarly journals Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen

2006 ◽  
Vol 395 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Thomas Pauquai ◽  
Julien Bouchoux ◽  
Danielle Chateau ◽  
Romain Vidal ◽  
Monique Rousset ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Subcellular Fractionation ◽  
Dietary Lipids ◽  
Protein Activity ◽  
Transfer Protein ◽  
Endoplasmic Reticulum Lumen ◽  
Mean Size ◽  
Low Glucose ◽  
Lipoprotein Assembly ◽  
Glucose Supply

Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia.

scholarly journals Association of the Golgi UDP-Galactose Transporter with UDP-Galactose:Ceramide Galactosyltransferase Allows UDP-Galactose Import in the Endoplasmic Reticulum

2003 ◽  
Vol 14 (8) ◽  
pp. 3482-3493 ◽  
Author(s):  
Hein Sprong ◽  
Sophie Degroote ◽  
Tommy Nilsson ◽  
Masao Kawakita ◽  
Nobuhiro Ishida ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Molecular Complex ◽  
Immunofluorescence Microscopy ◽  
Subcellular Fractionation ◽  
Intestinal Cells ◽  
Endoplasmic Reticulum Lumen ◽  
Double Label ◽  
Sizeable Fraction ◽  
Human Intestinal Cells

UDP-galactose reaches the Golgi lumen through the UDP-galactose transporter (UGT) and is used for the galactosylation of proteins and lipids. Ceramides and diglycerides are galactosylated within the endoplasmic reticulum by the UDP-galactose:ceramide galactosyltransferase. It is not known how UDP-galactose is transported from the cytosol into the endoplasmic reticulum. We transfected ceramide galactosyltransferase cDNA into CHOlec8 cells, which have a defective UGT and no endogenous ceramide galactosyltransferase. Cotransfection with the human UGT1 greatly stimulated synthesis of lactosylceramide in the Golgi and of galactosylceramide in the endoplasmic reticulum. UDP-galactose was directly imported into the endoplasmic reticulum because transfection with UGT significantly enhanced synthesis of galactosylceramide in endoplasmic reticulum membranes. Subcellular fractionation and double label immunofluorescence microscopy showed that a sizeable fraction of ectopically expressed UGT and ceramide galactosyltransferase resided in the endoplasmic reticulum of CHOlec8 cells. The same was observed when UGT was expressed in human intestinal cells that have an endogenous ceramide galactosyltransferase. In contrast, in CHOlec8 singly transfected with UGT 1, the transporter localized exclusively to the Golgi complex. UGT and ceramide galactosyltransferase were entirely detergent soluble and form a complex because they could be coimmunoprecipitated. We conclude that the ceramide galactosyltransferase ensures a supply of UDP-galactose in the endoplasmic reticulum lumen by retaining UGT in a molecular complex.

scholarly journals Augmentation of Ca2+-Induced Microsomal Triglyceride Transfer Protein Activity by Glucose Supply Enhances Hypertriglyceridemia in Vivo

2006 ◽  
Vol 29 (5) ◽  
pp. 889-895 ◽  
Author(s):  
Hyun-Jeong Cho ◽  
Hyo-Chan Kang ◽  
Young-Cheol Ju ◽  
Hyun-Sub Lee ◽  
Hyeong-Soo Kim ◽  
...  
Keyword(s):  
Microsomal Triglyceride Transfer Protein ◽  
Protein Activity ◽  
Transfer Protein ◽  
Glucose Supply

scholarly journals Relationship between phospholipid transfer protein activity and HDL level and size among inbred mouse strains

1999 ◽  
Vol 40 (2) ◽  
pp. 295-301 ◽  
Author(s):  
John J. Albers ◽  
Wendy Pitman ◽  
Gertrud Wolfbauer ◽  
Marian C. Cheung ◽  
Hal Kennedy ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Mouse Strains ◽  
Phospholipid Transfer Protein ◽  
Inbred Mouse Strains ◽  
Protein Activity ◽  
Transfer Protein ◽  
Phospholipid Transfer

scholarly journals Microsomal Triglyceride Transfer Protein Inhibition Induces Endoplasmic Reticulum Stress and Increases Gene Transcription via Ire1α/cJun to Enhance Plasma ALT/AST

2013 ◽  
Vol 288 (20) ◽  
pp. 14372-14383 ◽  
Author(s):  
Joby Josekutty ◽  
Jahangir Iqbal ◽  
Takao Iwawaki ◽  
Kenji Kohno ◽  
M. Mahmood Hussain
Keyword(s):  
Endoplasmic Reticulum ◽  
Free Cholesterol ◽  
Plasma Lipids ◽  
Microsomal Triglyceride Transfer Protein ◽  
Major Mechanism ◽  
Protein Inhibition ◽  
Transfer Protein ◽  
Oxidative Stresses ◽  
Triglyceride Rich Lipoprotein ◽  
Response To Stress

Microsomal triglyceride transfer protein (MTP) is a target to reduce plasma lipids because of its indispensable role in triglyceride-rich lipoprotein biosynthesis. MTP inhibition in Western diet fed mice decreased plasma triglycerides/cholesterol, whereas increasing plasma alanine/aspartate aminotransferases (ALT/AST) and hepatic triglycerides/free cholesterol. Free cholesterol accumulated in the endoplasmic reticulum (ER) and mitochondria resulting in ER and oxidative stresses. Mechanistic studies revealed that MTP inhibition increased transcription of the GPT/GOT1 genes through up-regulation of the IRE1α/cJun pathway leading to increased synthesis and release of ALT1/AST1. Thus, transcriptional up-regulation of GPT/GOT1 genes is a major mechanism, in response to ER stress, elevating plasma transaminases. Increases in plasma and tissue transaminases might represent a normal response to stress for survival.

scholarly journals Resynthesis of phosphatidylinositol in permeabilized neutrophils following phospholipase Cβ activation: transport of the intermediate, phosphatidic acid, from the plasma membrane to the endoplasmic reticulum for phosphatidylinositol resynthesis is not dependent on soluble lipid carriers or vesicular transport

1999 ◽  
Vol 341 (2) ◽  
pp. 435-444 ◽  
Author(s):  
Jacqueline WHATMORE ◽  
Claudia WIEDEMANN ◽  
Pennti SOMERHARJU ◽  
Philip SWIGART ◽  
Shamshad COCKCROFT
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Vesicular Transport ◽  
Human Neutrophils ◽  
Permeabilized Cells ◽  
Transfer Protein ◽  
Membrane Contact ◽  
Phosphatidylinositol Transfer ◽  
Pi Hydrolysis ◽  
Hydrolysis Of

Receptor-mediated phospholipase C (PLC) hydrolysis of phosphoinositides is accompanied by the resynthesis of phosphatidylinositol (PI). Hydrolysis of phosphoinositides occurs at the plasma membrane, and the resulting diacylglycerol (DG) is converted into phosphatidate (PA). Two enzymes located at the endoplasmic reticulum (ER) function sequentially to convert PA back into PI. We have established an assay whereby the resynthesis of PI could be followed in permeabilized cells. In the presence of [γ-32P]ATP, DG generated by PLC activation accumulates label when converted into PA. The 32P-labelled PA is subsequently converted into labelled PI. The formation of labelled PI reports the arrival of labelled PA from the plasma membrane to the ER. Cytosol-depleted, permeabilized human neutrophils are capable of PI resynthesis following stimulation of PLCβ (in the presence of phosphatidylinositol-transfer protein), provided that CTP and inositol are also present. We also found that wortmannin, an inhibitor of endocytosis, or cooling the cells to 15 °C did not stop PI resynthesis. We conclude that PI resynthesis is dependent neither on vesicular transport mechanisms nor on freely diffusible, soluble transport proteins. Phosphatidylcholine-derived PA generated by the ADP-ribosylation-factor-stimulated phospholipase D pathway was found to accumulate label, reflecting the rapid cycling of PA to DG, and back. This labelled PA was not converted into PI. We conclude that PA derived from the PLC pathway is selected for PI resynthesis, and its transfer to the ER could be membrane-protein-mediated at sites of close membrane contact.

scholarly journals Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community

2011 ◽  
Vol 29 (5) ◽  
pp. 863-868 ◽  
Author(s):  
Justin P Zachariah ◽  
Michael J Pencina ◽  
Asya Lyass ◽  
Guneet Kaur ◽  
Ralph B DʼAgostino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Protein Activity ◽  
Transfer Protein ◽  
Plasma Cholesteryl Ester
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