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Bakuchiol targets mitochondrial proteins, prohibitins and voltage-dependent anion channels: New insights into developing antiviral agents.
Shoji, Masaki; Esumi, Tomoyuki; Masuda, Takeshi; Tanaka, Narue; Okamoto, Risa; Sato, Hinako; Watanabe, Mihiro; Takahashi, Etsuhisa; Kido, Hiroshi; Ohtsuki, Sumio; Kuzuhara, Takashi.
Afiliação
  • Shoji M; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. Electronic address: masaki-shoji@ph.bunri-u.ac.jp.
  • Esumi T; Institute of Pharmacognosy Attached to Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • Masuda T; Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan.
  • Tanaka N; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • Okamoto R; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • Sato H; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • Watanabe M; Institute of Pharmacognosy Attached to Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • Takahashi E; Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
  • Kido H; Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
  • Ohtsuki S; Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Kuzuhara T; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. Electronic address: kuzuhara@ph.bunri-u.ac.jp.
J Biol Chem ; 300(2): 105632, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38199573
ABSTRACT
We previously reported that bakuchiol, a phenolic isoprenoid anticancer compound, and its analogs exert anti-influenza activity. However, the proteins targeted by bakuchiol remain unclear. Here, we investigated the chemical structures responsible for the anti-influenza activity of bakuchiol and found that all functional groups and C6 chirality of bakuchiol were required for its anti-influenza activity. Based on these results, we synthesized a molecular probe containing a biotin tag bound to the C1 position of bakuchiol. With this probe, we performed a pulldown assay for Madin-Darby canine kidney cell lysates and purified the specific bakuchiol-binding proteins with SDS-PAGE. Using nanoLC-MS/MS analysis, we identified prohibitin (PHB) 2, voltage-dependent anion channel (VDAC) 1, and VDAC2 as binding proteins of bakuchiol. We confirmed the binding of bakuchiol to PHB1, PHB2, and VDAC2 in vitro using Western blot analysis. Immunofluorescence analysis showed that bakuchiol was bound to PHBs and VDAC2 in cells and colocalized in the mitochondria. The knockdown of PHBs or VDAC2 by transfection with specific siRNAs, along with bakuchiol cotreatment, led to significantly reduced influenza nucleoprotein expression levels and viral titers in the conditioned medium of virus-infected Madin-Darby canine kidney cells, compared to the levels observed with transfection or treatment alone. These findings indicate that reducing PHBs or VDAC2 protein, combined with bakuchiol treatment, additively suppressed the growth of influenza virus. Our findings indicate that bakuchiol exerts anti-influenza activity via a novel mechanism involving these mitochondrial proteins, providing new insight for developing anti-influenza agents.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Fenóis / Influenza Humana Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Fenóis / Influenza Humana Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2024 Tipo de documento: Article