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Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell

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Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARδ and the activity of SMS. In his study, macrophage-induced foam cells were utilized to model important pathological changes that occur in AS. The influence of PPARδ agonism by GW501516 on SMS and its product molecule SM were measured. Results indicated that the activation of PPARδ was correlated in a positive manner with the activity of SMS2, and the content of SM was dose dependently increased by GW501516. Together, this study represents the first to suggest that PPARδ activation may be a potential risk of AS through enhancing activity of SMS2.

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Acknowledgments

This work was supported by Natural Science Foundation of Hubei Province of China, No. 2014CFB617.

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    1. Hubei University for Nationalities, Enshi, Hubei, 445000, China

      Dongsheng Mou

    2. Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China

      Hua Yang, Changhua Qu, Juan Chen & Chaogui Zhang

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    Dongsheng Mou and Hua Yang contributed equally to this work.

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    Mou, D., Yang, H., Qu, C. et al. Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell. Inflammation 39, 1538–1546 (2016). https://doi.org/10.1007/s10753-016-0389-0

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