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2014 ; 33
(12
): 839-46
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Mipu1 overexpression protects macrophages from oxLDL-induced foam cell formation
and cell apoptosis
#MMPMID25141035
Qu SL
; Fan WJ
; Zhang C
; Guo F
; Han D
; Pan WJ
; Li W
; Feng DM
; Jiang ZS
DNA Cell Biol
2014[Dec]; 33
(12
): 839-46
PMID25141035
show ga
Mipu1 (myocardial ischemic preconditioning upregulated protein 1) is a novel
N-terminal Kruppel-associated box (KRAB)/C2H2 zinc finger superfamily protein,
that displays a powerful effect in protecting H9c2 cells from oxidative
stress-induced cell apoptosis. The present study aims to investigate the effect
of Mipu1 overexpression on oxidized low-density lipoprotein (oxLDL)-induced foam
cell formation, cell apoptosis, and its possible mechanisms. New Zealand healthy
rabbits were used to establish atherosclerosis model, and serum levels of
triglycerides, total cholesterol, high-density lipoprotein cholesterol, and
low-density lipoprotein cholesterol were detected by an automatic biochemical
analyzer. Sudan IV staining was used to detect atherosclerotic lesions. The
RAW264.7 macrophage cell line was selected as the experimental material. Oil red
O staining, high-performance liquid chromatography, and Dil-labeled lipoprotein
were used to detect cholesterol accumulation qualitatively and quantitatively,
respectively. Flow cytometry was used to determine cell apoptosis. Real-time
quantitative polymerase chain reaction (PCR) was used to detect the mRNA
expression of the main proteins that are associated with the transport of
cholesterol, such as ABCA1, ABCG1, SR-BI, and CD36. Western blot analysis was
used to detect the protein expression of Mipu1. There were atherosclerotic
lesions in the high-fat diet group with Sudan IV staining. High-fat diet
decreased Mipu1 expression and increased CD36 expression significantly at the
10th week compared with standard-diet rabbits. Mipu1 overexpression decreased
oxLDL-induced cholesterol accumulation, oxLDL uptake, cell apoptosis, and cleaved
caspase-3. Mipu1 overexpression inhibited the oxLDL-induced CD36 mRNA and protein
expression, but it did not significantly inhibit the mRNA expression of ABCA1,
ABCG1, and SR-BI. Mipu1 overexpression inhibits oxLDL-induced foam cell formation
and cell apoptosis. Mipu1 overexpression reduces the lipid intake of macrophages
and might be associated with the downregulation of CD36 expression in the
presence of oxLDL.