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2 results on '"Takuto Murakami"'

1. Inhibitory effects of local anesthetics on the proteasome and their biological actions

Author

Udin Bahrudin, Masaki Unno, Kazuya Nishio, Akiko Kita, Peili Li, Masaru Kato, Masashi Inoue, Shunichi Tsujitani, Takuto Murakami, Rina Sugiyama, Yasushi Saeki, Yuji Obara, Keiji Tanaka, Hiroshi Yamaguchi, Isao Sakane, Yasushi Kawata, Toshiyuki Itoh, Haruaki Ninomiya, Ichiro Hisatome, and Yukio Morimoto

Subjects
Medicine, Science
Abstract

Abstract Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the β5 subunit of the 20S proteasome, and not to the other active subunits, β1 and β2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities. In addition, we confirmed that the aromatic ring of these LAs was critical for inhibiting the proteasome. These LAs stabilized p53 and suppressed proliferation of p53-positive but not of p53-negative cancer cells.

Published
2017
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2. Inhibitory effects of local anesthetics on the proteasome and their biological actions

Author

Yasushi Kawata, Isao Sakane, Keiji Tanaka, Peili Li, Hiroshi Yamaguchi, Udin Bahrudin, Yuji Obara, Masaki Unno, Haruaki Ninomiya, Yasushi Saeki, Toshiyuki Itoh, Kazuya Nishio, Ichiro Hisatome, Akiko Kita, Masashi Inoue, Yukio Morimoto, Takuto Murakami, Rina Sugiyama, Shunichi Tsujitani, and Masaru Kato

Subjects
0301 basic medicine, Proteasome Endopeptidase Complex, Leupeptins, Science, Protein subunit, Pilsicainide, Drug development, Antidepressant, 030204 cardiovascular system & hematology, Protein degradation, Biology, Pharmacology, Inhibitory postsynaptic potential, 20s proteasome, Article, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Animals, Humans, Anesthetics, Local, Cell Proliferation, Multidisciplinary, Protein Stability, Endoplasmic reticulum, Lidocaine, Recurrent depression, Kososan, Molecular Docking Simulation, 030104 developmental biology, Proteasome, Cancer cell, Medicine, Cattle, Molecular modelling, Social defeat stress, Proteasome Inhibitors, medicine.drug
Abstract

Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the β5 subunit of the 20S proteasome, and not to the other active subunits, β1 and β2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities. In addition, we confirmed that the aromatic ring of these LAs was critical for inhibiting the proteasome. These LAs stabilized p53 and suppressed proliferation of p53-positive but not of p53-negative cancer cells.

Published
2017
Full Text
View/download PDF

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