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Peroxisome proliferator-activated receptor α mediates enhancement of gene expression of cerebroside sulfotransferase in several murine organs

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Abstract

Sulfatides, 3-O-sulfogalactosylceramides, are known to have multifunctional properties. These molecules are distributed in various tissues of mammals, where they are synthesized from galactosylceramides by sulfation at C3 of the galactosyl residue. Although this reaction is specifically catalyzed by cerebroside sulfotransferase (CST), the mechanisms underlying the transcriptional regulation of this enzyme are not understood. With respect to this issue, we previously found potential sequences of peroxisome proliferator-activated receptor (PPAR) response element on upstream regions of the mouse CST gene and presumed the possible regulation by the nuclear receptor PPARα. To confirm this hypothesis, we treated wild-type and Ppara-null mice with the specific PPARα agonist fenofibrate and examined the amounts of sulfatides and CST gene expression in various tissues. Fenofibrate treatment increased sulfatides and CST mRNA levels in the kidney, heart, liver, and small intestine in a PPARα-dependent manner. However, these effects of fenofibrate were absent in the brain or colon. Fenofibrate treatment did not affect the mRNA level of arylsulfatase A, which is the key enzyme for catalyzing desulfation of sulfatides, in any of these six tissues. Analyses of the DNA-binding activity and conventional gene expression targets of PPARα has demonstrated that fenofibrate treatment activated PPARα in the kidney, heart, liver, and small intestine but did not affect the brain or colon. These findings suggest that PPARα activation induces CST gene expression and enhances sulfatide synthesis in mice, which suggests that PPARα is a possible transcriptional regulator for the mouse CST gene.

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Acknowledgment

This work was supported in part by G.L. Sciences (Tokyo, Japan).

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Metabolic Regulation, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Takero Nakajima, Yuji Kamijo, Huang Yuzhe, Takefumi Kimura, Naoki Tanaka, Eiko Sugiyama, Atsushi Hara & Toshifumi Aoyama

  2. Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

    Yuji Kamijo

  3. Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei, China

    Huang Yuzhe

  4. Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

    Takefumi Kimura

  5. Department of Nutritional Science, Nagano Prefectural College, Nagano, Nagano, Japan

    Eiko Sugiyama

  6. Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Minami-Minowa, Kami-Ina, Nagano, Japan

    Kozo Nakamura

  7. Division of Microbiology and Molecular Cell Biology, Nihon Pharmaceutical University, Ina, Kita-Adachi, Saitama, Japan

    Mamoru Kyogashima

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  1. Takero Nakajima
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  2. Yuji Kamijo
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  10. Toshifumi Aoyama
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Correspondence to Yuji Kamijo.

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Nakajima, T., Kamijo, Y., Yuzhe, H. et al. Peroxisome proliferator-activated receptor α mediates enhancement of gene expression of cerebroside sulfotransferase in several murine organs. Glycoconj J 30, 553–560 (2013). https://doi.org/10.1007/s10719-012-9454-6

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