2022/11/01 更新

写真a

ハラダ　ユイカ
原田　結加
HARADA Yuika
所属
自然生命科学研究支援センター 助教（特任）
職名
助教（特任）
外部リンク

学位

  • 博士（薬科学） （ 2018年3月   岡山大学 ）

研究キーワード

  • トランスポーター

研究分野

  • ライフサイエンス / 薬系衛生、生物化学

 

論文

  • Vesicular nucleotide transporter is a molecular target of eicosapentaenoic acid for neuropathic and inflammatory pain treatment. 査読 国際誌

    Yuri Kato, Kengo Ohsugi, Yuto Fukuno, Ken Iwatsuki, Yuika Harada, Takaaki Miyaji

    Proceedings of the National Academy of Sciences of the United States of America   119 ( 30 )   e2122158119   2022年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Eicosapentaenoic acid (EPA), an omega-3 (ω-3) polyunsaturated fatty acid, is an essential nutrient that exhibits antiinflammatory, neuroprotective, and cardiovascular-protective activities. Although EPA is used as a nutrient-based pharmaceutical agent or dietary supplement, its molecular target(s) is debatable. Here, we showed that EPA and its metabolites strongly and reversibly inhibit vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and release of adenosine triphosphate (ATP) in purinergic chemical transmission. In vitro analysis showed that EPA inhibits human VNUT-mediated ATP uptake at a half-maximal inhibitory concentration (IC50) of 67 nM, acting as an allosteric modulator through competition with Cl-. EPA impaired vesicular ATP release from neurons without affecting the vesicular release of other neurotransmitters. In vivo, VNUT-/- mice showed a delay in the onset of neuropathic pain and resistance to both neuropathic and inflammatory pain. EPA potently attenuated neuropathic and inflammatory pain in wild-type mice but not in VNUT-/- mice without affecting the basal nociception. The analgesic effect of EPA was canceled by the intrathecal injection of purinoceptor agonists and was stronger than that of existing drugs used for neuropathic pain treatment, with few side effects. Neuropathic pain impaired insulin sensitivity in previous studies, which was improved by EPA in the wild-type mice but not in the VNUT-/- mice. Our results showed that VNUT is a molecular target of EPA that attenuates neuropathic and inflammatory pain and insulin resistance. EPA may represent a unique nutrient-based treatment and prevention strategy for neurological, immunological, and metabolic diseases by targeting purinergic chemical transmission.

    DOI： 10.1073/pnas.2122158119

    PubMed

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  • Vesicular nucleotide transporter mediates ATP release and migration in neutrophils 査読

    Yuika Harada, Yuri Kato, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   293 ( 10 )   3770 - 3779   2018年3月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

    DOI： 10.1074/jbc.m117.810168

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  • Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells 査読

    Tomoya Takeuchi, Yuika Harada, Satomi Moriyama, Kazuyuki Furuta, Satoshi Tanaka, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   292 ( 9 )   3909 - 3918   2017年3月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

    DOI： 10.1074/jbc.m116.756197

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  • Identification of a mammalian vesicular polyamine transporter 査読

    Miki Hiasa, Takaaki Miyaji, Yuka Haruna, Tomoya Takeuchi, Yuika Harada, Sawako Moriyama, Akitsugu Yamamoto, Hiroshi Omote, Yoshinori Moriyama

    Scientific Reports   4 ( 1 )   2014年10月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

    DOI： 10.1038/srep06836

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    その他リンク： http://www.nature.com/articles/srep06836

  • Immunological Identification of Vesicular Nucleotide Transporter in Intestinal L Cells 査読

    Yuika Harada, Miki Hiasa

    Biological and Pharmaceutical Bulletin   37 ( 7 )   1090 - 1095   2014年

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Pharmaceutical Society of Japan  

    DOI： 10.1248/bpb.b14-00275

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