Inhibitory effects of local anesthetics on the proteasome and their biological actions.
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ABSTRACT:
SUBMITTER: Bahrudin U
PROVIDER: S-EPMC5506043 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Inhibitory effects of local anesthetics on the proteasome and their biological actions.
Bahrudin Udin U Unno Masaki M Nishio Kazuya K Kita Akiko A Li Peili P Kato Masaru M Inoue Masashi M Tsujitani Shunichi S Murakami Takuto T Sugiyama Rina R Saeki Yasushi Y Obara Yuji Y Tanaka Keiji K Yamaguchi Hiroshi H Sakane Isao I Kawata Yasushi Y Itoh Toshiyuki T Ninomiya Haruaki H Hisatome Ichiro I Morimoto Yukio Y
Scientific reports 20170711 1
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 no ...[more]
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