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Article

Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1

  • Authors:
    • Hidetoshi Fujita
    • Satoko Aratani
    • Naoko Yagishita
    • Kusuki Nishioka
    • Toshihiro Nakajima
  • View Affiliations / Copyright

    Affiliations: Institute of Medical Science, Tokyo Medical University, Tokyo 160‑8402, Japan, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216‑8511, Japan
  • Pages: 5701-5708
    |
    Published online on: October 23, 2018
       https://doi.org/10.3892/mmr.2018.9576
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Abstract

Synoviolin (Syvn1), an E3 ubiquitin ligase in endoplasmic reticulum‑associated protein degradation, is involved in rheumatoid arthritis, fibrosis, liver cirrhosis and obesity. We previously demonstrated that Syvn1 negatively regulates the function of peroxisome proliferator‑activated receptor gamma coactivator‑1β (PGC‑1β). In addition, treatment with a Syvn1 inhibitor suppressed weight gain in a mouse model of obesity by activating PGC‑1β via Syvn1 inhibition. It has been suggested that the Syvn1 inhibitors may have therapeutic benefits in obese patients. The present study tested the inhibitory activity of walnut extract, a natural product, on Syvn1 activity. Walnut extract inhibited the effect of Syvn1 on the cell proliferation of rheumatoid synovial cells and repressed the interaction between PGC‑1β and Syvn1 in an in vitro binding assay. Polyubiquitination of PGC‑1β by Syvn1 was suppressed by walnut extract in a concentration‑dependent manner, but walnut extract did not have an inhibitory effect on the autoubiquitination of Syvn1. Treatment with walnut extract in mouse embryonic fibroblasts increased the number of mitochondria, suggesting that exposure to the extract recovered PGC‑1β function. These results demonstrated that constituents of walnut extract may serve as lead compounds in drug development efforts aiming to produce drugs to treat patients with obesity and obesity‑associated metabolic diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Fujita H, Aratani S, Yagishita N, Nishioka K and Nakajima T: Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Mol Med Rep 18: 5701-5708, 2018.
APA
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., & Nakajima, T. (2018). Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Molecular Medicine Reports, 18, 5701-5708. https://doi.org/10.3892/mmr.2018.9576
MLA
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., Nakajima, T."Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1". Molecular Medicine Reports 18.6 (2018): 5701-5708.
Chicago
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., Nakajima, T."Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1". Molecular Medicine Reports 18, no. 6 (2018): 5701-5708. https://doi.org/10.3892/mmr.2018.9576
Copy and paste a formatted citation
x
Spandidos Publications style
Fujita H, Aratani S, Yagishita N, Nishioka K and Nakajima T: Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Mol Med Rep 18: 5701-5708, 2018.
APA
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., & Nakajima, T. (2018). Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Molecular Medicine Reports, 18, 5701-5708. https://doi.org/10.3892/mmr.2018.9576
MLA
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., Nakajima, T."Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1". Molecular Medicine Reports 18.6 (2018): 5701-5708.
Chicago
Fujita, H., Aratani, S., Yagishita, N., Nishioka, K., Nakajima, T."Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1". Molecular Medicine Reports 18, no. 6 (2018): 5701-5708. https://doi.org/10.3892/mmr.2018.9576
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