title: Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.
abstract: Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226.
authors: Facultad de Ciencias Médicas, Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, Universidad Nacional de La Plata, La Plata, Argentina.
authors: Juan D
authors: JD
authors: Toledo
authors: Horacio A
authors: HA
authors: Garda
authors: Laura V
authors: LV
authors: Cabaleiro
authors: Angela
authors: A
authors: Cuellar
authors: Magali
authors: M
authors: Pellon-Maison
authors: Maria R
authors: MR
authors: Gonzalez-Baro
authors: Marina C
authors: MC
authors: Gonzalez
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D010743:Phospholipids; D014280:Triglycerides; C095606:apolipoprotein A-I Helsinki; D002784:Cholesterol; C506641:Acat1 protein, mouse; D000101:Acetyl-CoA C-Acetyltransferase