PMID- 22648616
OWN - NLM
STAT- MEDLINE
DCOM- 20121207
LR  - 20181201
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Linking)
VI  - 56
IP  - 5
DP  - 2012 May
TI  - Molecular mechanism of curcumin on the suppression of cholesterol accumulation in 
      macrophage foam cells and atherosclerosis.
PG  - 691-701
LID - 10.1002/mnfr.201100735 [doi]
AB  - SCOPE: Curcumin, a potent antioxidant extracted from Curcuma longa, confers 
      protection against atherosclerosis, yet the detailed mechanisms are not fully 
      understood. In this study, we examined the effect of curcumin on lipid 
      accumulation and the underlying molecular mechanisms in macrophages and 
      apolipoprotein E-deficient (apoE(-)/(-)) mice. METHODS AND RESULTS: Treatment with 
      curcumin markedly ameliorated oxidized low-density lipoprotein (oxLDL)-induced 
      cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake 
      and increased cholesterol efflux. In addition, curcumin decreased the protein 
      expression of scavenger receptor class A (SR-A) but increased that of ATP-binding 
      cassette transporter (ABC) A1 and had no effect on the protein expression of 
      CD36, class B receptor type I (SR-BI), or ATP-binding cassette transporter G1 
      (ABCG1). The downregulation of SR-A by curcumin was via 
      ubiquitin-proteasome-calpain-mediated proteolysis. Furthermore, the 
      curcumin-induced upregulation of ABCA1 was mainly through calmodulin-liver X 
      receptor alpha (LXRalpha)-dependent transcriptional regulation. Curcumin administration 
      modulated the expression of SR-A, ABCA1, ABCG1, and SR-BI in aortas and retarded 
      atherosclerosis in apoE(-)/(-) mice. CONCLUSION: Our findings suggest that inhibition 
      of SR-A-mediated oxLDL uptake and promotion of ABCA1-dependent cholesterol efflux 
      are two crucial events in suppression of cholesterol accumulation by curcumin in 
      the transformation of macrophage foam cells.
CI  - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Zhao, Jing-Feng
AU  - Zhao JF
AD  - Department of Physiology, National Yang-Ming University, Taipei, Taiwan.
FAU - Ching, Li-Chieh
AU  - Ching LC
FAU - Huang, Yu-Chu
AU  - Huang YC
FAU - Chen, Chien-Yu
AU  - Chen CY
FAU - Chiang, An-Na
AU  - Chiang AN
FAU - Kou, Yu Ru
AU  - Kou YR
FAU - Shyue, Song-Kun
AU  - Shyue SK
FAU - Lee, Tzong-Shyuan
AU  - Lee TS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Apolipoproteins E)
RN  - 0 (CD36 Antigens)
RN  - 0 (Calmodulin)
RN  - 0 (Lipoproteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Liver X Receptors)
RN  - 0 (Nr1h3 protein, mouse)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class A)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 0 (oxidized low density lipoprotein)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.4.22.- (Calpain)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology
MH  - Apolipoprotein A-I/metabolism
MH  - Apolipoproteins E/genetics/metabolism
MH  - Atherosclerosis/drug therapy/genetics/metabolism/prevention & control
MH  - CD36 Antigens/metabolism
MH  - Calmodulin/metabolism
MH  - Calpain/metabolism
MH  - Cholesterol/*metabolism
MH  - Curcumin/*pharmacology
MH  - Foam Cells/*drug effects/*metabolism
MH  - Lipid Metabolism/drug effects
MH  - Lipoproteins/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Liver X Receptors
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Orphan Nuclear Receptors/genetics/metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Scavenger Receptors, Class A/metabolism
MH  - Scavenger Receptors, Class B/metabolism
EDAT- 2012/06/01 06:00
MHDA- 2012/12/12 06:00
CRDT- 2012/06/01 06:00
PHST- 2012/06/01 06:00 [entrez]
PHST- 2012/06/01 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
AID - 10.1002/mnfr.201100735 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2012 May;56(5):691-701. doi: 10.1002/mnfr.201100735.