INVESTIGADORES
PELLON MAISON Magali
artículos
Título:
Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation
Autor/es:
JUAN D TOLEDO; HORACIO A GARDA; LAURA V CABALEIRO; ANGELA CUELLAR; PELLON MAISON, MAGALI; GONZALEZ-BARO, MR; GONZALEZ MARINA
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: New York; Año: 2013 vol. 377 p. 197 - 205
ISSN:
0300-8177
Resumen:
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
DK107) 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 DK107,
but not with wild-type apoA-I or a variant containing a
similar deletion at the C-terminal region (DK226), 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 DK107 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 DK107 or DK226.
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 DK107,
but not with wild-type apoA-I or a variant containing a
similar deletion at the C-terminal region (DK226), 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 DK107 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 DK107 or DK226.
DK107,
but not with wild-type apoA-I or a variant containing a
similar deletion at the C-terminal region (DK226), 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 DK107 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 DK107 or DK226.
DK226), 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 DK107 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 DK107 or DK226.
DK107 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 DK107 or DK226.DK107 or DK226.