Document Detail


Effect of cyclosporine and sirolimus on fatty acid desaturase activities in cultured HEPG2 cells.
MedLine Citation:
PMID:  19545746     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present work was to evaluate the influence of cyclosporine (CsA) and sirolimus (SRL) on fatty acid (FA) desaturase activities. These enzymes (named Delta9, Delta6, and Delta5 desaturases) catalyze reactions leading to the biosynthesis of n-9, n-6, and n-3 FA families. n-3 FA family, derived from alpha-linolenic acid, is involved in the prevention of vascular events, which appear after successful kidney transplantation. Five groups of HepG(2) cells in culture were treated with either CsA (1 microg/microL and 2 microg/microL) or SRL (10 ng/mL and 20 ng/mL) for 3 days, including a control group without immunosuppressive treatment. We studied the incorporation and metabolic conversion of radioactive [1-(14)C]palmitic, linoleic, and eicosatrienoic acids. We also analyzed fatty acid composition. The distribution of radioactive metabolic products after incubation of these cells with [1-(14)C]palmitic acid revealed a decrease in Delta9 desaturase activity in the presence of each immunosuppressive drug: CsA = 0.61 +/- 0.01; SRL = 0.59 +/- 0.04 versus control = 0.79 +/- 0.05 (P < .01). We observed a significant increase in Delta6 and Delta5 desaturase activities under the influence of the immunosuppressive drugs: radiolabeled linoleic acid (CsA: 0.93 +/- 0.04; SRL: 1.02 +/- 0.03 vs control 0.60 +/- 0.03; P < .01) and eicosatrienoic acid (CsA: 1.12 +/- 0.02; SRL: 1.07 +/- 0.01 vs control 0.75 +/- 0.01; P < .01). In conclusion, CsA and SRL modulated the biosynthesis of polyunsaturated FAs, decreasing Delta9 desaturase and increasing Delta6 and Delta5 desaturase activities.
Authors:
N Lausada; I N T de Gómez Dumm; J C Raimondi; M J T de Alaniz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation proceedings     Volume:  41     ISSN:  1873-2623     ISO Abbreviation:  Transplant. Proc.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-23     Completed Date:  2009-09-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1865-70     Citation Subset:  IM    
Affiliation:
Facultad de Ciencias Médicas, Instituto de Investigaciones Bioquímicas de La Plata, Universidad Nacional de La Plata. nlausada@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acids / metabolism
Carcinoma, Hepatocellular
Cell Line, Tumor
Cyclosporine / pharmacology*
Fatty Acid Desaturases / drug effects,  metabolism*
Fatty Acids / metabolism
Humans
Immunosuppressive Agents / pharmacology
Kinetics
Linoleic Acid / metabolism
Liver Neoplasms
Palmitic Acid / metabolism
Sirolimus / pharmacology*
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Fatty Acids; 0/Immunosuppressive Agents; 2197-37-7/Linoleic Acid; 53123-88-9/Sirolimus; 57-10-3/Palmitic Acid; 59865-13-3/Cyclosporine; EC 1.14.19.-/Fatty Acid Desaturases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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