Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models expressing fatty acid desaturases.
Experimental evidence has suggested that plasma membrane (PM)-associated signaling and hence cell metabolism and viability depend on lipid composition and organization. The aim of the present work is to develop a cell model to study the endogenous polyunsaturated fatty acids (PUFAs) effect on PM properties and analyze its influence on cholesterol (Chol) homeostasis. We have previously shown that by using a cell line over-expressing stearoyl-CoA-desaturase, membrane composition and organization coordinate cellular pathways involved in Chol efflux and cell viability by different mechanisms. Now, we expanded our studies to a cell model over-expressing both Δ5 and Δ6 desaturases, which resulted in a permanently higher PUFA content in PM. Furthermore, this cell line showed increased PM fluidity, Chol storage, and mitochondrial activity. In addition, human apolipoprotein A-I-mediated Chol removal was less efficient in these cells than in the corresponding control. Taken together, our results suggested that the cell functionality is preserved by regulating PM organization and Chol exportation and homeostasis.
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), La Plata 1900, Buenos Aires, Argentina.
María S
MS
Jaureguiberry
M Alejandra
MA
Tricerri
Susana A
SA
Sanchez
Gabriela S
GS
Finarelli
Mauro A
MA
Montanaro
Eduardo D
ED
Prieto
Omar J
OJ
Rimoldi
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D008563:Membrane Lipids; D002784:Cholesterol; D044943:Fatty Acid Desaturases
cholesterol transport; cytotoxicity; fatty acid desaturases; human apolipoprotein A-I; membrane heterogeneity