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Mitochondrial Cholesterol Transporter, StAR, Inhibits Human THP-1 Monocyte-Derived Macrophage Apoptosis

  • Original Article
  • Published:
Lipids

Abstract

Steroidogenic acute regulatory protein (StAR) plays an important role in the maintenance of intracellular lipid homeostasis. Macrophages are the key cellular player in the pathophysiology of atherosclerosis. Imbalance of macrophage lipid homeostasis causes cellular apoptosis, which is the key process in the initiation of atherosclerosis. The present study has investigated the effects of StAR in the apoptotic process of human THP-1 derived macrophages induced by serum withdrawal or Ox-LDL. Overexpression of StAR significantly decreased the number of apoptotic macrophages by decreasing the expression of pro-apoptotic genes Caspase-3 and Bax mRNA and protein levels, as well as through increasing expression of anti-apoptotic gene Bcl-2 mRNA and protein levels in the absence and presence of Ox-LDL. The results indicate that StAR plays an important role in macrophage and foam cell apoptotic processing, which may provide a potential method for preventing atherosclerosis.

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Abbreviations

ABCG1:

ATP-binding cassette transporter G1

ApoE−/−:

Apolipoprotein E-deficient

Bax:

BCL2-associated X protein

Bcl-2:

B cell lymphoma/leukemia-2

CYP27A1:

Sterol 27-hydroxylase

EGFP:

Enhanced green fluorescence protein

FC:

Free cholesterol

FCM:

Flow cytometry

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

IMM:

Inner mitochondrial membrane

LDL:

Low-density lipoprotein

LXRα:

Liver X receptor alpha

MOI:

Multiplicity of infection

OMM:

Outer mitochondrial membrane

Ox-LDL:

Oxidized low-density lipoprotein

PE:

Phycoerythrin

PMA:

Phorbol 12-myristate 13-acetate

PPARγ:

Proliferation peroxysome activator receptor gamma

P450scc:

Side-chain cleavage cytochrome P450

StAR:

Steroidogenic acute regulatory protein

THP-1:

Human, peripheral blood, leukemia, acute monocytic

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

7-ADD:

7-Amino-actinomycin

25HC:

25-Hydroxycholesterol

25HC3S:

Sulfated 25-hydroxycholesterol

27HC:

27-Hydroxycholesterol

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC 30871021 and NSFC 30800547).

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, P.O. Box 224, 138 Yixueyuan Road, 200032, Shanghai, People’s Republic of China

    Qianming Bai, Xiaobo Li, Yanxia Ning, Fengdi Zhao & Lianhua Yin

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  1. Qianming Bai
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  2. Xiaobo Li
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  3. Yanxia Ning
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Correspondence to Lianhua Yin.

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Bai, Q., Li, X., Ning, Y. et al. Mitochondrial Cholesterol Transporter, StAR, Inhibits Human THP-1 Monocyte-Derived Macrophage Apoptosis. Lipids 45, 29–36 (2010). https://doi.org/10.1007/s11745-009-3375-6

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  • DOI: https://doi.org/10.1007/s11745-009-3375-6

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