Effect of cyclosporine and sirolimus on fatty acid desaturase activities in cultured HEPG2 cells.
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.
Lausada
N
N
Facultad de Ciencias Médicas, Instituto de Investigaciones Bioquímicas de La Plata, Universidad Nacional de La Plata. nlausada@gmail.com
de Gómez Dumm
I N T
IN
Raimondi
J C
JC
de Alaniz
M J T
MJ
D001095:Arachidonic Acids / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007700:Kinetics; D019787:Linoleic Acid / Q000378:metabolism; D008113:Liver Neoplasms; D019308:Palmitic Acid / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*
D001095:Arachidonic Acids; D005227:Fatty Acids; D007166:Immunosuppressive Agents; D019308:Palmitic Acid; D016572:Cyclosporine; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D020123:Sirolimus