Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na⁺/K⁺-ATPase

• Okina Yuji

  Department of Applied Biology, Kyoto Institute of Technology

• Takeuchi Fumihiko

  Department of Applied Biology, Kyoto Institute of Technology

• Yokomichi Tomonobu

  Department of Applied Biology, Kyoto Institute of Technology

• Takada Yohei

  Center for Biological Resources and Informatics, Tokyo Institute of Technology

• Kataoka Takao

  Department of Applied Biology, Kyoto Institute of Technology Center for Biological Resources and Informatics, Tokyo Institute of Technology

書誌事項

タイトル別名

• Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na⁺/K⁺-ATPase

抄録

Cardiac glycosides, which are inhibitors of Na⁺/K⁺-ATPase, are classified into cardenolides and bufadienolides. We have recently shown that two cardenolide glycosides, ouabain and odoroside A, inhibit Na⁺/K⁺-ATPase, thereby preventing nuclear factor κB-inducible protein expression by blocking Na⁺-dependent amino acid transport. In this study, we investigated the mechanism of action of cardenolide aglycones in tumor necrosis factor α (TNF-α)-induced gene expression. Ouabagenin, digitoxigenin, and digoxigenin were found to inhibit the TNF-α-induced cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) in human lung carcinoma A549 cells. Those cardenolide aglycones did not inhibit the TNF-α-induced expression of ICAM-1 mRNA, but strongly inhibited the TNF-α-induced expression of ICAM-1 as translation product. The inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin, digitoxigenin, and digoxigenin was significantly reversed by the ectopic expression of ouabain-resistant rat Na⁺/K⁺-ATPase α1 isoform. Moreover, knockdown of Na⁺/K⁺-ATPase α1 isoform augmented the inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin or ouabain. These results clearly indicate that cardenolide aglycones inhibit the TNF-α-induced ICAM-1 expression at the translation step by blocking Na⁺/K⁺-ATPase.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (1), 39-47, 2015

  公益社団法人 日本薬学会

キーワード

• cardenolide aglycone
• tumor necrosis factor α
• intercellular adhesion molecule-1
• Na⁺/K⁺-ATPase
• cardiac glycoside
• ouabagenin

詳細情報

• CRID: 1390001204631234944
• NII論文ID: 130004872236
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00532
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026000815
• PubMed: 25744456
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026000815
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/1/38_b14-00532/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015261397
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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