title: Ursolic Acid Inhibits Na+/K+-ATPase Activity and Prevents TNF-α-Induced Gene Expression by Blocking Amino Acid Transport and Cellular Protein Synthesis.
abstract: Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, induce the expression of a wide variety of genes, including intercellular adhesion molecule-1 (ICAM-1). Ursolic acid (3β-hydroxy-urs-12-en-28-oic acid) was identified to inhibit the cell-surface ICAM-1 expression induced by pro-inflammatory cytokines in human lung carcinoma A549 cells. Ursolic acid was found to inhibit the TNF-α-induced ICAM-1 protein expression almost completely, whereas the TNF-α-induced ICAM-1 mRNA expression and NF-κB signaling pathway were decreased only partially by ursolic acid. In line with these findings, ursolic acid prevented cellular protein synthesis as well as amino acid uptake, but did not obviously affect nucleoside uptake and the subsequent DNA/RNA syntheses. This inhibitory profile of ursolic acid was similar to that of the Na+/K+-ATPase inhibitor, ouabain, but not the translation inhibitor, cycloheximide. Consistent with this notion, ursolic acid was found to inhibit the catalytic activity of Na+/K+-ATPase. Thus, our present study reveals a novel molecular mechanism in which ursolic acid inhibits Na+/K+-ATPase activity and prevents the TNF-α-induced gene expression by blocking amino acid transport and cellular protein synthesis.
authors: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. yokkon424@yahoo.co.jp.
authors: Tomonobu
authors: T
authors: Yokomichi
authors: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. morikyon-073128@m2.gyao.ne.jp.
authors: Kyoko
authors: K
authors: Morimoto
authors: Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. nana.ooshima@to.shiseido.co.jp.
authors: Nana
authors: N
authors: Oshima
authors: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. yamada239@sekisui.jp.
authors: Yuriko
authors: Y
authors: Yamada
authors: Graduate School of Science and Technology, Niigata University, Igarashi 2-8501, Nishi-ku, Niigata 950-2181, Japan. fu-liwei@mgc.co.jp.
authors: Liwei
authors: L
authors: Fu
authors: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. taketani@kit.ac.jp.
authors: Shigeru
authors: S
authors: Taketani
authors: Department of Chemistry and Chemical Engineering, Niigata University, Ikarashi 2-8501, Nishi-ku, Niigata 950-2181, Japan. andomasa2@ksj.biglobe.ne.jp.
authors: Masayoshi
authors: M
authors: Ando
authors: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. takao.kataoka@kit.ac.jp.
authors: Takao
authors: T
authors: Kataoka