Cholesterol homeostasis depends on membrane lipid composition

JAUREGUIBERRY MS, FINARELLI GS, TRICERRI MA, RIMOLDI OJ

Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Cholesterol homeostasis is crucial for cell viability, but specially, its removal from peripheral cells is critical in order to prevent its accumulation on the artery wall. High density lipoproteins (HDL) and their major apolipoprotein apoA-I, play a key role in the Reverse Cholesterol Transport, which results in the removal of cholesterol (Chol) excess, and its transport towards the liver. It is well-known that this process is dependent on the activation of the ABCA1 transporter. Here we suggest that membrane composition and/or organization is also strongly involved in cholesterol homeostasis. In order to test this hypothesis, we constructed a cell line overexpressing Stearoyl CoA desaturase, (SCD-cells, SAIB 2007), which results in the enrichment of monounsaturated fatty acids in the plasma membrane, without altering ABCA1 levels. Now we characterize membrane composition and analyze lipid removal, caveolin-1 expression and cell viability mediated by apoA-I. Our results show that plasma membrane is slightly enriched in Chol but has a lower phospholipids/sphingomyelin ratio in SCD-cells, which show less-efficient Chol removal mediated by apoA-I. Instead, these cells export more caveolin to the medium, and are more resistant to Chol toxicity. We discuss our results in terms of a dynamic equilibrium between cell viability and Chol homeostasis.