Current Search:   Thibeaux, Simeon (x)

View All Items

  • CSV Spreadsheet
(1 - 2 of 2)
HEPATIC LIPASE REGULATES LIPOPROTEIN TRAFFICKING IN HEPATOCYTES
Title
HEPATIC LIPASE REGULATES LIPOPROTEIN TRAFFICKING IN HEPATOCYTES.
Creator
Thibeaux, Simeon, Siddiqi, Shadab, University of Central Florida
Abstract / Description
The production of very low density lipoprotein and high density lipoprotein particles by the liver is a tightly regulated process, which begins with synthesis and assembly of core protein components in the rough endoplasmic reticulum. Factors influencing the production and metabolism of these particles are of immediate medical relevance, as their malfunction or hyperactivity can lead to an assortment of disease states. Hepatic lipase is a secreted liver enzyme, with many previously described...
Show moreThe production of very low density lipoprotein and high density lipoprotein particles by the liver is a tightly regulated process, which begins with synthesis and assembly of core protein components in the rough endoplasmic reticulum. Factors influencing the production and metabolism of these particles are of immediate medical relevance, as their malfunction or hyperactivity can lead to an assortment of disease states. Hepatic lipase is a secreted liver enzyme, with many previously described roles in the metabolism and clearance of both high and low density lipoproteins. Increased production and assembly of this enzyme is an indicator of metabolic dysfunction, while its absence or insufficiency leads to pre-mature atherosclerosis and death. The present study shows that this enzyme's role in lipoprotein metabolism is not confined to the degradation and clearance of these particles after they have been secreted. Experiments using co-immunoprecipitation targeted at hepatic lipase demonstrate that this protein interacts with ApoA1 and ApoB100, the core protein components of HDL and VLDL respectively, at the ER level in hepatocytes, as part of an enormous multi-subunit protein complex. This interaction with ApoA1 leads to decreased competence of hepatocytes to secrete HDL, which confers a pro-atherogenic phenotype. Analysis of ER to Golgi VLDL transport vesicles, produced with a cell-free in vitro budding assay, has revealed that hepatic lipase is co-secreted between these compartments with immature VLDL particles. Further analysis of cytosol isolated from hepatocytes demonstrates an interaction between hepatic lipase and the LDL-receptor related protein in a post-Golgi vesicle; the significance of which will be investigated in future studies.
Show less
Date Issued
2015
Identifier
CFH0004736, ucf:45366
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFH0004736
Cathepsin B Regulates VLDL Secretion Through LFABP Cleavage
Title
Cathepsin B Regulates VLDL Secretion Through LFABP Cleavage.
Creator
Thibeaux, Simeon, Siddiqi, Shadab, Kim, Yoon-Seong, Teter, Kenneth, University of Central Florida
Abstract / Description
The liver is tasked with managing the concentration of various metabolites in the blood, and of particular importance is the uptake of free fatty-acid (FFA), as elevated concentrations of FFA are toxic to cells. FFAs are transported across the cell membrane by CD36 and distributed by LFABP to the endoplasmic reticulum (ER), where they are esterified to glycerol, yielding more chemically inert triglyceride (TAG), which is essential to the process of VLDL assembly. VLDL secretion distributes...
Show moreThe liver is tasked with managing the concentration of various metabolites in the blood, and of particular importance is the uptake of free fatty-acid (FFA), as elevated concentrations of FFA are toxic to cells. FFAs are transported across the cell membrane by CD36 and distributed by LFABP to the endoplasmic reticulum (ER), where they are esterified to glycerol, yielding more chemically inert triglyceride (TAG), which is essential to the process of VLDL assembly. VLDL secretion distributes energy rich TAG to peripheral tissues, and its dysfunction leads to hepatic steatosis, which may progress into hepatocellular carcinoma. The present study examined the role of cathepsin B (CatB) in regulating very-low density lipoprotein (VLDL) secretion through liver fatty-acid binding protein (LFABP) cleavage as well as CD36 expression in response to 0.5 mM oleic acid:BSA treatment, which has been reported to redistribute CatB from the lysosome to the cytosol, where the majority of cellular LFABP is localized. Genetic knock-down of CatB in McA-RH7777 cells resulted in increased VLDL secretion as measured by 3H TAG DPM counting and immunoblot for ApoB in cell culture media, due to increased expression of LFABP and CD36 and increased FFA uptake. Knock-down of CatB also resulted in decreased cellular TAG as measured by 3H DPM counting due to increased VLDL secretion. CatB over-expression in McA-RH7777 cells resulted in decreased FFA uptake leading to decreased VLDL secretion, which was due to increased cleavage of LFABP. Co-localization of LFABP and CatB was observed exclusively under conditions of 0.5 mM oleic acid:BSA treatment. Based on these results, we can conclude that CatB plays a distinct physiological role in the turnover of LFABP and CD36 protein, which leads to suppressed uptake of FFA, and thus, reduced TAG synthesis and VLDL secretion.
Show less
Date Issued
2017
Identifier
CFE0006669, ucf:51236
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0006669