[Ghrelin down-regulates ACAT-1 in THP-1 derived foam cells via growth hormone secretagogue receptor-dependent pathway].
OBJECTIVE
To investigate the effects of Ghrelin on the expression of acyl coenzyme A:cholesterol acyltransferases-1 (ACAT-1) in THP-1 derived foam cells.


METHODS
The human monocytic leukemia cell line (THP-1) was chosen in our study. The differentiation of THP-1 cells into macrophages was induced by phorbol 12-myristate 13-acetate. Macrophages were then incubated with oxidized LDL (ox-LDL) to generate foam cells. Ghrelin and [D-Lys3]-GHRP-6, the special antagonist of growth hormone secretagogue receptor (GHS-R), were treated during foam cells formation. The ACAT-1 protein and mRNA levels were detected by Western blot and RT-PCR. The effect of variance of cholesterol content was measured by zymochemistry via-fluorospectrophotometer.


RESULTS
Ghrelin reduced the content of cholesterol ester in foam cells obviously. ACAT-1 protein and mRNA levels were also decreased. The antagonist of GHS-R inhibited the effects of Ghrelin on ACAT-1 expression in dose-dependent manner. The ACAT-1 mRNA levels of the GHS-R specific antagonist groups (10(-5), 5 x 10(-5), 10(-4) mol/L) were 1.14 +/- 0.04, 1.58 +/- 0.03, 2.40 +/- 0.16, significantly higher than that of the Ghrelin group (0.89 +/- 0.05). And the protein expressions were 1.25 +/- 0.09, 1.77 +/- 0.11, 2.30 +/- 0.09, also higher than that of the Ghrelin group (0.86 +/- 0.08).


CONCLUSIONS
Ghrelin might interfere atherosclerosis by down-regulating the expression of ACAT-1 via GHS-R pathway.
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Jing-Jing
JJ
Wan
Bei
B
Cheng
Yan-Fu
YF
Wang
Chun-Li
CL
Mei
Wei
W
Liu
Li
L
Ke
Ping
P
He
D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D005487:Foam Cells / Q000378:metabolism*; D054439:Ghrelin / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013053:Spectrophotometry
D000214:Acyl Coenzyme A; D054439:Ghrelin; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D002784:Cholesterol; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase