Delta-K107: A natural variant of apolipoprotein A-I promotes differential cellular responses

GONZALEZ MC; TOLEDO JD; CABALEIRO LV; CUELLAR LA; GARDA HA

Potrero de Los Funes, San Luis

Congreso; 47th Annual Meeting Argentine Society for Biochemistry and Molecular Biology XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Apolipoprotein A-I (apoA-I) is the major protein in the high density lipoproteins (HDL), and it plays a relevant role in the antiatherogenic reverse cholesterol transport. ApoA-I have tworepeats with a particular type Y charge distribution, which have been proposed as key role players in the apoA-I mediated cell lipid efflux. Patients carrying an apoA-I variant with a single deletion at the central type Y helical region (DK107) have an impaired HDL metabolism and increased atherogenic risk. To know if the cellular responses to DK107 are altered we have compared the behavior of DK107 with wild type apoA-I and another variant with a deleted Lysine (DK226) in the C-terminal type Y helical repeat. Macrophages RAW 264.7 stimulated with the different proteins were used for comparing the expression and intracellular cholesterol (Chol) pool available for esterification by acyl CoA cholesterol acyl transferase (ACAT). Also we have evaluated theefflux of choline-phospholipids (PL) as well as sphingomyelin (SM) and Phosphatidylcholine (PC) intracellular content. We have detected that DK107, but not DK226, increased ACAT protein level in different Chol loading conditions (0, 10 or 50, µg/ml Chol). However, only a slight ACAT activity increase is produced by Dk107 with low Chol load condition. All the proteins were active in promoting PL efflux.