2.P.71 NK-104, a potent HMGCoA-reductase inhibitor, increases intracellular degradation of apo B-100 and decreases its secretion in HepG2 cells

1997 ◽  
Vol 134 (1-2) ◽  
pp. 131
Author(s):  
C. Ooyen ◽  
A.M. Bersino ◽  
A.L. Catapano
Keyword(s):  
Hepg2 Cells ◽  
Reductase Inhibitor ◽  
Apo B ◽  
Hmgcoa Reductase ◽  
Intracellular Degradation ◽  
Hmgcoa Reductase Inhibitor

2.P.79 Cholesteryl ester storage disease: Molecular defects and treatment with the HMGCoA-reductase inhibitor lovastatin

1997 ◽  
Vol 134 (1-2) ◽  
pp. 132-133
Author(s):  
F. Rassoul ◽  
E. Keller ◽  
A. Naumann ◽  
P. Lohse ◽  
K. Purschwitz ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Reductase Inhibitor ◽  
Storage Disease ◽  
Hmgcoa Reductase ◽  
Molecular Defects ◽  
Hmgcoa Reductase Inhibitor

Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells

2001 ◽  
Vol 353 (3) ◽  
pp. 493-501 ◽  
Author(s):  
Wei LIAO ◽  
Lawrence CHAN
Keyword(s):  
Apolipoprotein B ◽  
Hepg2 Cells ◽  
Proteasome Inhibitor ◽  
Plasma Lipoproteins ◽  
Apo B ◽  
Net Production ◽  
Lipoprotein Particles ◽  
Essential Component ◽  
Intracellular Degradation

Apolipoprotein (apo) B-100 is an essential component of atherogenic plasma lipoproteins. Previous studies have demonstrated that the production of apoB-100 is regulated largely by intracellular degradation at both the co-translational and post-translational levels and that proteasome-mediated and non-proteasome-mediated pathways are involved in this process. ApoB-100 is a glycoprotein. The present study was undertaken to address the question of whether the inhibition of N-linked glycosylation with tunicamycin would interfere with apoB-100 production. We demonstrated that the treatment of HepG2 cells with tunicamycin decreased the net production of apoB-100 by enhancing co-translational degradation of the protein. This effect of tunicamycin was partly prevented by lactacystin, a specific proteasome inhibitor. Because lactacystin only partly reversed the effects of tunicamycin on apoB biogenesis, tunicamycin seemed also to induce apoB co-translational degradation in HepG2 cells by one or more non-proteasomal pathways. Furthermore, tunicamycin increased apoB ubiquitination approx. 4-fold. The proportion of the newly synthesized apoB-100 that was secreted and incorporated into the nascent lipoprotein particles was unaffected by tunicamycin. Thus the tunicamycin-mediated inhibition of N-linked glycosylation interferes with the production of apoB-100 that is mediated by both proteasomal and non-proteasomal pathways.

Is fat restriction needed with HMGCoA reductase inhibitor treatment?

1992 ◽  
Vol 93 (1-2) ◽  
pp. 59-70 ◽  
Author(s):  
Peter M. Clifton ◽  
Marion B. Wight ◽  
Paul J. Nestel
Keyword(s):  
Reductase Inhibitor ◽  
Hmgcoa Reductase ◽  
Hmgcoa Reductase Inhibitor ◽  
Inhibitor Treatment

833 HCV-REPLICATING HEPG2 CELLS PRODUCE INFECTIOUS APO-E POSITIVE, BUT APO-B NEGATIVE HYBRID PARTICLES

2012 ◽  
Vol 56 ◽  
pp. S325
Author(s):  
B. Jammart ◽  
M. Michelet ◽  
B. Bartosch ◽  
R. Parent ◽  
F. Zoulim ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Hybrid Particles ◽  
Apo B ◽  
Apo E

scholarly journals DNase I- and micrococcal nuclease-hypersensitive sites in the human apolipoprotein B gene are tissue specific.

1988 ◽  
Vol 8 (1) ◽  
pp. 71-80 ◽  
Author(s):  
B Levy-Wilson ◽  
C Fortier ◽  
B D Blackhart ◽  
B J McCarthy
Keyword(s):  
Hela Cells ◽  
Apolipoprotein B ◽  
Hepg2 Cells ◽  
Transcriptional Start Site ◽  
Dnase I ◽  
Micrococcal Nuclease ◽  
Apo B ◽  
Human Apolipoprotein ◽  
Hypersensitive Sites ◽  
High Degree

We have mapped the DNase I- and micrococcal nuclease-hypersensitive sites present in the 5' end of the human apolipoprotein B (apo-B) gene in nuclei from cells expressing or not expressing the gene. Four DNase I-hypersensitive sites were found in nuclei from liver-derived HepG2 cells and intestine-derived CaCo-2 cells, which express the apo-B gene, but not in HeLa cells, which do not. These sites are located near positions -120, -440, -700, and +760 base pairs relative to the transcriptional start site. Undifferentiated CaCo-2 cells exhibited another site, near position -540. Six micrococcal nuclease-hypersensitive sites were found in nuclei from HepG2 and CaCo-2 cells, but not in HeLa cells or free DNA. These sites are located near positions -120, -390, -530, -700, -850, and +210. HepG2 cells exhibited another site, near position +460. Comparison of the DNA sequence of the 5' flanking regions of the human and mouse apo-B genes revealed a high degree of evolutionary conservation of short stretches of sequences in the immediate vicinity of each of the DNase I- and most of the micrococcal nuclease-hypersensitive sites.

scholarly journals Effect of reduced low-density lipoprotein receptor level on HepG2 cell cholesterol metabolism

1998 ◽  
Vol 329 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Lahoucine IZEM ◽  
Eric RASSART ◽  
Lassana KAMATE ◽  
Louise FALSTRAULT ◽  
David RHAINDS ◽  
...  
Keyword(s):  
Hepg2 Cell ◽  
Hepg2 Cells ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Constitutive Expression ◽  
Density Lipoprotein ◽  
Low Density ◽  
Apo B ◽  
Acat Activity

Low-density lipoproteins (LDL) are taken up by both LDL receptor (LDLr)-dependent and -independent pathways. In order to determine the importance of these pathways in the activity of the various enzymes that are important in maintaining the cellular cholesterol level in hepatic cells, we created HepG2 cells expressing lower levels of LDLr. Thus HepG2 cells were transfected with a constitutive expression vector (pRc/CMV) containing a fragment of LDLr cDNA inserted in an antisense manner. Stable transformants were obtained that showed significant reductions of 42, 72 and 85% of LDLr protein levels compared with the control, as demonstrated by immunoblotting and confirmed by the LDL binding assay. The best inactivation was achieved with the construct containing the first 0.7 kb of LDLr cDNA. Incubating the different HepG2 cell subtypes with LDL showed similar association of apolipoprotein B (apo B) or cholesteryl esters from LDL with the cells, indicating that the LDLr deficiency did not significantly affect LDL uptake by the cell. However, apoB degradation was reduced significantly by 71-82% in the most LDLr-deficient HepG2 cells. We also found that 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA red) activity is significantly increased by 32-35% in HepG2 cells expressing very low levels of LDLr that also demonstrate a significant decrease of 20% in acyl-CoA:cholesterol acyltransferase (ACAT) activity. However, these effects are moderate compared with those observed when cells were incubated in lipoprotein-depleted medium, where a > 900% increase in HMGCoA red activity and a loss of 60% of ACAT activity was observed. Thus, in HepG2 cells, different levels of LDLr affect LDL-apoB degradation, but have very little effect on LDL association, HMGCoA red and ACAT activities, revealing that LDLr is more important in the clearance of LDL-apoB than in HepG2 cell cholesterol homoeostasis, a role that should be attributable to both LDLr-dependent and -independent pathways.

scholarly journals Lovastatin: a new “ancient” molecule for hypercholesterolaemia/dyslipidaemia treatment

2008 ◽  
Vol 2 (2) ◽  
pp. 63-74
Author(s):  
Gianlorenzo Imperiale ◽  
Claudio Marengo
Keyword(s):  
Reductase Inhibitor ◽  
Cardiovascular Prevention ◽  
Lipid Lowering ◽  
Eligibility Criteria ◽  
Italian National Health Service ◽  
Clinical Benefits ◽  
Italian National Health ◽  
Hmgcoa Reductase Inhibitor ◽  
Secondary Cardiovascular Prevention

Lovastatin is the first HMGCoA-reductase inhibitor used for the control of hypercholesterolaemia (USA, 1987). In Italy, it’s been authorized for the therapy of hypercholesterolaemia/dyslipidaemia since end 2005. Several studies, conducted both in primary and in secondary cardiovascular prevention, underline the favourable profile in reducing the risk for ischaemic events and their complications. This molecule has the capability to reduce plasmatic atherogenic lipids levels enough to induce clinical benefits. The safety and tolerability of lovastatin are proved even for high dosages, as well as for long term use. Pharmacoeconomic evaluations have shown the value of its choice, in particular for patients who need lipid-lowering treatment but don’t satisfy eligibility criteria for reimbursement by the Italian National Health Service, as outlined by AIFA in 2005.

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