RRC ID 36758
著者 Okina Y, Takeuchi F, Yokomichi T, Takada Y, Kataoka T.
タイトル Cardenolide aglycones inhibit tumor necrosis factor α-induced expression of intercellular adhesion molecule-1 at the translation step by blocking Na⁺/K⁺-ATPase.
ジャーナル Biol Pharm Bull
Abstract 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.
巻・号 38(1)
ページ 39-47
公開日 2015-1-1
DOI 10.1248/bpb.b14-00532
PMID 25744456
MeSH Animals Cell Line Cell Line, Tumor Cell Survival / drug effects Digitoxigenin / pharmacology* Digoxigenin / pharmacology* Humans Intercellular Adhesion Molecule-1 / genetics Intercellular Adhesion Molecule-1 / metabolism* Ouabain / analogs & derivatives* Ouabain / pharmacology Protein Biosynthesis / drug effects RNA, Messenger / metabolism RNA, Small Interfering / genetics Rats Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors* Sodium-Potassium-Exchanging ATPase / genetics Sodium-Potassium-Exchanging ATPase / metabolism Tumor Necrosis Factor-alpha / metabolism*
IF 1.863
引用数 4
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 Hep G2(RCB1648) 3Y1-B clone 1-6(RCB0488)