Differential cellular responses to delta K107, a natural mutant of human apolipoprotein A-I

TOLEDO, J. D.; CABALEIRO, L. V.; GONZALEZ, M. C.; GARDA, H. A.

Buzios- Brasil

Congreso; VII Iberoamerican Congress of Biophysics; 2009

International Society of Biophysics

Apolipoprotein A-I (apoAI) is the major protein of high density lipoproteins (HDL) and plays a relevant role in antiatherogenic reverse cholesterol transport. This protein is mainly constituted by type A amphipathic a-helical repeats although there are two repeats with a particular type Y charge distribution, one at the centre and the other at the C-end, which have been proposed as playing a key role in the apoAI mediated cell lipid efflux. Patients carrying an apoAI variant with a single deletion at the central type Y helical region (DK107) have an altered HDL metabolism and increased atherogenic risk. This single deletion could alter the helix registry and modify the lipid binding properties and/or the interaction with cellular proteins of the central type Y apoAI domain. To know if the cellular responses to DK107 are altered, as well as to test the functional role of the central Y helical domain, the behavior of DK107 was compared with wild type apoAI and a mutant where the equivalent residue at the C-end type Y helical repeat was deleted (DK226). Here, we present partial results about the responses to these apoAI variants of two cellular lines: murine macrophages RAW 264.7 and chinese hamster ovary cells (CHOK1). At least in CHOK1 cells, DK107 has an impaired ability to evoke cholesterol mobilization from cholesteryl ester depots and recently synthesized pools. As detected in RAW cells, DK107, but not DK226, increases the cellular amount of acyl-CoA acy transferase (ACAT) protein. Both mutants, however, have a normal activity to promote cholesterol efflux in both cellular lines.