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Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells

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Abstract

To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.

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Abbreviations

IFN-γ:

Interferon-gamma

CVD:

Cardiovascular disease

CAD:

Coronary artery disease

ox-LDL:

Oxidized low-density lipoprotein

ROS:

Reactive oxygen species

RCT:

Reverse cholesterol transport

HDLs:

High-density lipoproteins

ABC:

ATP cassette binding transporters

apoAI:

Apolipoprotein A-I

LXR:

Liver X receptor

PMA:

Phorbol-12-myristate-13-acetate

CRP:

C-reactive protein

GX sPLA(2):

Group X secretory phospholipase A2

COX-2:

Cyclooxygenase 2

JNK:

c-Jun N-terminal kinase

PI3K:

Phosphatidylinositol 3-kinase

JAK:

Phosphatidylinositol 3-kinase

STAT1:

Transducer and activator of transcription 1

ERs:

Estrogen receptors

PPARs:

Peroxisome proliferator activated receptors

PGC-1:

PPAR gamma co-activator 1

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Acknowledgments

We wish to thank Institute of Cardiovascular Research for kindly providing us with THP-1 cells. We are grateful to Dr. Chao-ke Tang (Institute of Cardiovascular Research, University of South China, Hunan, China) for helpful suggestions and technical support.

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Authors and Affiliations

  1. Affiliated Hospital of Shaoyang Medical College, Shaoyang, 422000, Hunan, China

    Jin-quan Yan

  2. First People’s Hospital of Shaoyang City, Shaoyang, 422000, Hunan, China

    Chun-zhi Tan, Bin-yuan Zeng, Yu-ping Jiang, Jin Nie, Wei Liu, Qin Liu & Hao Dai

  3. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China

    Chun-zhi Tan

  4. The Second Affiliated Hospital of Nanhua University, Hengyang, 421001, Hunan, China

    Jin-hua Wu

  5. Hunan Province Geriatric Hospital, Changsha, 410000, Hunan, China

    Dong-cui Zhang

  6. No. 3 Hospital of Wuhan, Wuhan, 430000, Hubei, China

    Ji-ling Chen

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  1. Jin-quan Yan
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Correspondence to Chun-zhi Tan.

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Yan, Jq., Tan, Cz., Wu, Jh. et al. Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells. Mol Cell Biochem 379, 123–131 (2013). https://doi.org/10.1007/s11010-013-1634-6

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  • DOI: https://doi.org/10.1007/s11010-013-1634-6

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