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Your search keyword '"Atsushi Shibuta"' showing total 2 results
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2 results on '"Atsushi Shibuta"'

1. A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia

Author

Tsukasa Shimauchi, Takuro Numaga-Tomita, Yuri Kato, Hiroyuki Morimoto, Kosuke Sakata, Ryosuke Matsukane, Akiyuki Nishimura, Kazuhiro Nishiyama, Atsushi Shibuta, Yutoku Horiuchi, Hitoshi Kurose, Sang Geon Kim, Yasuteru Urano, Takashi Ohshima, and Motohiro Nishida

Subjects
canonical transient receptor potential 6, peripheral arterial disease, vessel maturation, 1-benzilpiperadine, Cytology, QH573-671
Abstract

Retarded revascularization after progressive occlusion of large conductance arteries is a major cause of bad prognosis for peripheral artery disease (PAD). However, pharmacological treatment for PAD is still limited. We previously reported that suppression of transient receptor potential canonical (TRPC) 6 channel activity in vascular smooth muscle cells (VSMCs) facilitates VSMC differentiation without affecting proliferation and migration. In this study, we found that 1-benzilpiperadine derivative (1-BP), a selective inhibitor for TRPC3 and TRPC6 channel activities, induced VSMC differentiation. 1-BP-treated mice showed increased capillary arterialization and improvement of peripheral circulation and skeletal muscle mass after hind-limb ischemia (HLI) in mice. 1-BP had no additive effect on the facilitation of blood flow recovery after HLI in TRPC6-deficient mice, suggesting that suppression of TRPC6 underlies facilitation of the blood flow recovery by 1-BP. 1-BP also improved vascular nitric oxide bioavailability and blood flow recovery after HLI in hypercholesterolemic mice with endothelial dysfunction, suggesting the retrograde interaction from VSMCs to endothelium. These results suggest that 1-BP becomes a potential seed for PAD treatments that target vascular TRPC6 channels.

Published
2022
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2. Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

Author

Taishi Higashi, Keiichi Motoyama, Takashi Ohshima, Nozomi Sugimoto, Masatoshi Fujita, Hidetaka Kosako, Hidetoshi Arima, Masaki Yukuhiro, Takuya Yokoyama, Kazumasa Yoshida, Hiroyuki Morimoto, Chika Tanaka, Atsushi Shibuta, Kazunari Sankoda, Risa Fujiwara, and Yuka Iwasaki

Subjects
Cell Survival, Mice, Nude, lcsh:Medicine, Antineoplastic Agents, Importin, Biochemistry, Article, Polyethylene Glycols, HeLa, Mice, chemistry.chemical_compound, Affinity chromatography, In vivo, Animals, Humans, Moiety, lcsh:Science, Cancer, Cell Proliferation, Multidisciplinary, biology, Drug discovery, Carbazole, lcsh:R, HCT116 Cells, beta Karyopherins, biology.organism_classification, Chemical biology, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Nuclear Pore Complex Proteins, Oncology, chemistry, Colonic Neoplasms, lcsh:Q, Antimitotic Agent, Lead compound, HeLa Cells
Abstract

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.

Published
2019

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