High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts.
The precise role of monounsaturated fatty acid (MUFA) synthesis in cell proliferation and programmed cell death remains unknown. The strong correlation of high levels of MUFA and neoplastic phenotype suggest that the regulation of stearoyl CoA desaturase (SCD) must play a significant role in cancer development. In this study, the levels of SCD protein and activity were investigated in normal (WI38) and SV40-transformed (SV40-WI38) human lung fibroblasts. Thus, the activity of SCD on exogenous [14C]stearic acid and endogenous [14C]acetate-labeled fatty acids was increased by 2.2- and 2.6-fold, respectively, in SV40-WI38 compared to WI38 fibroblasts. Concomitantly, a 3.3-fold increase in SCD protein content was observed in SV40-transformed cells. Cell transformation also led to high levels of MUFA, which was paralleled by a more fluid membrane environment. Furthermore, the levels of PPAR-gamma, a well-known activator of SCD expression, were highly increased in SV40-transformed fibroblasts. SCD activity appeared linked to the events of programmed cell death, since incubations with 40 microM etoposide induced apoptosis in SV40 cells, and led to a decrease in fatty acid synthesis, SCD activity and in MUFA cellular levels. Taken together, these results suggest that SCD protein and activity levels are associated with the events of neoplastic cell transformation and programmed cell death.
Scaglia
Natalia
N
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET-UNLP), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, calles 60 y 120, 1900 La Plata, Argentina. aigal@atlas.med.unlp.edu.ar
Caviglia
J Matías
JM
Igal
R Ariel
RA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D005047:Etoposide / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D005229:Fatty Acids, Monounsaturated; D008563:Membrane Lipids; D047495:PPAR gamma; D005047:Etoposide; D013230:Stearoyl-CoA Desaturase