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Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells

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Abstract

Consumption of fruits and vegetables is generally regarded as beneficial to plasma lipid profile. The mechanism by which the plant foods induce desirable lipid changes remains unclear. SREBP-2 is crucial in cholesterol metabolism, and it is a major regulator of the cholesterol biosynthesis enzyme HMGCR. Our lab has previously illustrated that apigenin and luteolin could attenuate the nuclear translocation of SREBP-2 through an AMPK-dependent pathway. In the present study, these two flavones were studied for their ability to deter the same in an AMPK-independent signaling route. The processing of SREBP-2 protein was promoted by phorbol 12-myristate 13-acetate (PMA) in the hepatic cells WRL and HepG2, and the increased processing was reversed by apigenin or luteolin co-administration. EMSA results demonstrated that the PMA-induced DNA-binding activity was weakened by the flavones. The increased amount of nuclear SREBP-2 in cells was attenuated by the flavonoid as shown by immunocytochemical imaging. Quantitative reverse transcriptase-polymerase chain reaction assay demonstrated that the transcription of HMGCR under both flavone treatments was reduced. However, apigenin appeared to be stronger than luteolin in restraining PMA-induced HMGCR mRNA expression. Since PMA is a diacylglycerol analog, these findings might have some physiological implications.

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Abbreviations

CVD:

Cardiovascular disease

RT-PCR:

Reverse transcriptase-polymerase chain reaction

EMSA:

Electromobility shift assay

SRE:

Sterol responsive element

SREBP:

Sterol regulatory element-binding proteins

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Acknowledgments

This study was supported by the Chinese University of Hong Kong Direct Grant Project (Grant # 4053047).

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    Authors and Affiliations

    1. Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong

      Yan Qin Tan, Tsz Yan Wong & Lai K. Leung

    2. Biochemistry Programmes, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong

      Lai K. Leung

    3. Department of Food Science, National Chiayi University, Chiayi City, Taiwan, ROC

      Shu-mei Lin

    4. Food and Nutritional Sciences/Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Rm.507C MMW Bldg, Shatin, N.T., Hong Kong

      Lai K. Leung

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    1. Yan Qin Tan
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    Correspondence to Lai K. Leung.

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    Yan Qin Tan and Tsz Yan Wong have contributed equally to this study.

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    Tan, Y.Q., Wong, T.Y., Lin, Sm. et al. Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells. Mol Cell Biochem 424, 163–172 (2017). https://doi.org/10.1007/s11010-016-2851-6

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