Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FC333366) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or norm...

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Main Authors: Marleen M.J. van Greevenbroek, Vicky M.M-J. Vermeulen, Tjerk W.A. de Bruin
Format: Article
Language:English
Published: Elsevier 2002-11-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520327590
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author Marleen M.J. van Greevenbroek
Vicky M.M-J. Vermeulen
Tjerk W.A. de Bruin
author_facet Marleen M.J. van Greevenbroek
Vicky M.M-J. Vermeulen
Tjerk W.A. de Bruin
author_sort Marleen M.J. van Greevenbroek
collection DOAJ
description The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FC333366) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or normolipidemic controls. Overall protein secretion was 10–15% higher after incubation with FCHL plasma. This was specifically caused by an increase in four secreted proteins, with estimated sizes of 240, 180, 120, and <40 kD (P < 0.001, P < 0.006, P < 0.002, P < 0.02, respectively). The 240 kD protein in the secretion proteome was identified as fibronectin by mass spectrometry. Plasma fibronectin concentrations were elevated in FCHL patients, confirming biological relevance of these data. Overall protein secretion by HepG2 cells correlated with concentrations of triglycerides (r = 0.61, P < 0.001) in the applied plasma samples. VLDL+IDL isolated from FCHL patients, induced a higher protein secretion than lipoproteins isolated from controls (P < 0.001). Remarkably, secretion of apoB, the structural protein of VLDL, was stimulated to a similar extent by FCHL and control plasma.FCHL plasma did not induce excess secretion of apoB by HepG2 cells compared with control plasma. FCHL plasma did stimulate secretion of several distinct hepatic proteins, among which fibronectin was identified.
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spelling doaj.art-c2f7b6094dd5491197903266c7c1cfaa2022-12-21T23:18:54ZengElsevierJournal of Lipid Research0022-22752002-11-01431118461854Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cellsMarleen M.J. van Greevenbroek0Vicky M.M-J. Vermeulen1Tjerk W.A. de Bruin2Laboratory for Molecular Metabolism and Endocrinology, Maastricht University, Maastricht, The NetherlandsLaboratory for Molecular Metabolism and Endocrinology, Maastricht University, Maastricht, The NetherlandsLaboratory for Molecular Metabolism and Endocrinology, Maastricht University, Maastricht, The NetherlandsThe aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FC333366) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or normolipidemic controls. Overall protein secretion was 10–15% higher after incubation with FCHL plasma. This was specifically caused by an increase in four secreted proteins, with estimated sizes of 240, 180, 120, and <40 kD (P < 0.001, P < 0.006, P < 0.002, P < 0.02, respectively). The 240 kD protein in the secretion proteome was identified as fibronectin by mass spectrometry. Plasma fibronectin concentrations were elevated in FCHL patients, confirming biological relevance of these data. Overall protein secretion by HepG2 cells correlated with concentrations of triglycerides (r = 0.61, P < 0.001) in the applied plasma samples. VLDL+IDL isolated from FCHL patients, induced a higher protein secretion than lipoproteins isolated from controls (P < 0.001). Remarkably, secretion of apoB, the structural protein of VLDL, was stimulated to a similar extent by FCHL and control plasma.FCHL plasma did not induce excess secretion of apoB by HepG2 cells compared with control plasma. FCHL plasma did stimulate secretion of several distinct hepatic proteins, among which fibronectin was identified.http://www.sciencedirect.com/science/article/pii/S0022227520327590hepatic lipoproteins fibronectinHepG2familial combined hyperlipidemiatriglycerides
spellingShingle Marleen M.J. van Greevenbroek
Vicky M.M-J. Vermeulen
Tjerk W.A. de Bruin
Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
Journal of Lipid Research
hepatic lipoproteins fibronectin
HepG2
familial combined hyperlipidemia
triglycerides
title Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
title_full Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
title_fullStr Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
title_full_unstemmed Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
title_short Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells
title_sort familial combined hyperlipidemia plasma stimulates protein secretion by hepg2 cells
topic hepatic lipoproteins fibronectin
HepG2
familial combined hyperlipidemia
triglycerides
url http://www.sciencedirect.com/science/article/pii/S0022227520327590
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AT tjerkwadebruin familialcombinedhyperlipidemiaplasmastimulatesproteinsecretionbyhepg2cells