Document Detail

Cyclosporine inhibits catabolism of low-density lipoproteins in HepG2 cells by about 25%.
MedLine Citation:
PMID:  8781333     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to elucidate the possible causes of elevated low-density lipoprotein (LDL)-cholesterol levels in transplanted patients treated with the immunosuppressant drug, cyclosporine. HepG2 cells, from a well-differentiated cell-line of hepatoma cells, were cultured and used as a model for in vitro hepatocytic LDL uptake. Different concentrations of cyclosporine, which were within the range of concentrations found in humans treated with cyclosporine, were added to tissue culture medium together with 125I-LDL. The results showed that cyclosporine reduced LDL uptake and degradation in HepG2 cells by about 25%. The cells were also pretreated with cyclosporine for 1 to 24 hours and then incubated with new medium containing labeled LDL for 2 hours at 4 degrees C in an LDL-binding assay. The data showed that cyclosporine reduced the subsequent LDL binding. Cyclosporine has no toxic effects on HepG2 cells, as shown by unchanged growth capacity of the cells. By means of a 50-fold excess of unlabeled LDL, a monoclonal anti-LDL receptor antibody, and dextran sulfate, we also evaluated if this inhibition of LDL binding occurred through the LDL receptor-mediated pathway, through non-LDL receptor-mediated pathways, or through both. The results show that cyclosporine reduces LDL binding and uptake by mainly inhibiting the LDL receptor-mediated pathway. We also studied the effect of the LDL-cyclosporine complex on the binding of labelled LDL. The presence of cyclosporine in the LDL particle does not influence the binding behaviour of LDL to its receptor. We also found that cyclosporine reduces the expression of the LDL receptor messenger RNA (mRNA) by about 40%. Thus, the interpretation of this study is that cyclosporine can cause an increase in LDL-cholesterol in the plasma of transplantation patients by reducing the catabolism of LDL in the liver by inhibiting mainly the LDL receptor-mediated catabolism through an effect on LDL receptor synthesis.
O A Rayyes; A Wallmark; C H Florén
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  24     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-12-04     Completed Date:  1996-12-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  613-9     Citation Subset:  IM    
Department of Medicine, Malmo University Hospital, Sweden.
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MeSH Terms
Carcinoma, Hepatocellular / metabolism*,  pathology
Cyclosporine / metabolism,  pharmacology*
Lipoproteins, LDL / antagonists & inhibitors*,  metabolism,  pharmacokinetics
Liver Neoplasms / metabolism*,  pathology
RNA, Messenger / metabolism
Receptors, LDL / genetics,  metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Lipoproteins, LDL; 0/RNA, Messenger; 0/Receptors, LDL; 59865-13-3/Cyclosporine

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