Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo-gamma-linoleic and alpha-linolenic acids in A549 cells.
It is well known that simvastatin affects cholesterol synthesis. Furthermore it inhibits growth and proliferation and perturbs fatty acid metabolism in some cell lines. We have studied the effects of simvastatin on the uptake and metabolism of exogenous fatty acid in the human lung adenocarcinoma A549 cells. Simvastatin inhibited the proliferation of A549, and caused an increment in phospholipid/cholesterol ratio due to an increment in phospholipid content without affecting cholesterol content. All the fatty acids were uptaken and metabolized in both control and treated cells. The conversion of palmitic, linoleic and dihomo-gamma-linoleic acids to their metabolites and products/precursor ratios for the desaturation and elongation reactions showed that simvastatin enhanced the Delta5 desaturation step and altered some elongating steps. The machinery for unsaturated fatty acid synthesis in A549 is quite sensitive to simvastatin and its effects could have important implication taking into account that highly unsaturated fatty acids are involved in the regulation of diverse cellular functions by themselves or through their metabolites.
Instituto de Investigaciones Bioqui;micas de La Plata (INIBIOLP), CONICET-UNLP, Facultad de Ciencias Médicas, Calle 60 y 120, La Plata 1900, Argentina.
M J
MJ
Bellini
M P
MP
Polo
M J T
MJ
de Alaniz
M G
MG
de Bravo
D000230:Adenocarcinoma; D000924:Anticholesteremic Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D019787:Linoleic Acid / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms; D019308:Palmitic Acid / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D019821:Simvastatin / Q000378:metabolism* / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000378:metabolism*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D017962:alpha-Linolenic Acid; D019308:Palmitic Acid; D002784:Cholesterol; D019787:Linoleic Acid; D019821:Simvastatin