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Title: Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons

Abstract

CCG-1423, a chemical inhibitor of Rho signaling, blocks serum response factor (SRF)/megakaryoblastic leukemia 1 (MKL1)-mediated gene expression by inhibiting the nuclear accumulation of MKL1. Several studies have suggested that CCG-1423 interacts not only with MKL1, which has a critical role in the regulation of neuronal morphology, but also with phosphatase and actin regulator 1 (Phactr1), which is localized at synapses. However, the effect of CCG-1423 on neuronal cells, especially on neuronal morphology, remains to be determined. In this study, we focused on the effect of CCG-1423 on axonal elongation, dendritic length, dendritic complexity and dendritic spine morphology. Incubation of cortical neuron cultures with up to 10 μM CCG-1423 for 72 h did not significantly affect cell viability. CCG-1423 inhibited axonal elongation and blocked the increase of dendritic length and complexity, but did not affect dendritic spine morphology. Here, we demonstrated for the first time that CCG-1423 affects neurite elongation, except for dendritic spines, without affecting neuronal cell viability. This study provides a better understanding of the effects of CCG-1423 on neurons, which may be useful for the assessment of the potential clinical application of CCG-1423 and its derivatives. - Highlights: • CCG-1423 does not affect neuronal cell viability. • CCG-1423 inhibits axonalmore » elongation in rat cortical neurons. • CCG-1423 decreases dendritic complexity in a time-dependent manner.« less

Authors:
; ;  [1];  [1];  [1];  [1];  [1];  [1]
  1. Laboratory of Molecular Neurobiology, Graduate School of Medicine & Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)
Publication Date:
OSTI Identifier:
22719113
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 492; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; BROMIDES; DENDRITES; ELONGATION; LEUKEMIA; MICROTUBULES; MORPHOLOGY; NERVE CELLS; PHOSPHATASES; RATS; TIME DEPENDENCE; TRANSCRIPTION; TRANSCRIPTION FACTORS; VERTEBRAE

Citation Formats

Kikuchi, Keietsu, Shiota, Jun, Yamada, Tetsuya, Ishikawa, Mitsuru, Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Ihara, Daisuke, Fukuchi, Mamoru, Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Tsuda, Masaaki, and Tabuchi, Akiko. Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.08.071.
Kikuchi, Keietsu, Shiota, Jun, Yamada, Tetsuya, Ishikawa, Mitsuru, Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Ihara, Daisuke, Fukuchi, Mamoru, Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Tsuda, Masaaki, & Tabuchi, Akiko. Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons. United States. doi:10.1016/J.BBRC.2017.08.071.
Kikuchi, Keietsu, Shiota, Jun, Yamada, Tetsuya, Ishikawa, Mitsuru, Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Ihara, Daisuke, Fukuchi, Mamoru, Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Tsuda, Masaaki, and Tabuchi, Akiko. Sat . "Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons". United States. doi:10.1016/J.BBRC.2017.08.071.
@article{osti_22719113,
title = {Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons},
author = {Kikuchi, Keietsu and Shiota, Jun and Yamada, Tetsuya and Ishikawa, Mitsuru and Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 and Ihara, Daisuke and Fukuchi, Mamoru and Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 and Tsuda, Masaaki and Tabuchi, Akiko},
abstractNote = {CCG-1423, a chemical inhibitor of Rho signaling, blocks serum response factor (SRF)/megakaryoblastic leukemia 1 (MKL1)-mediated gene expression by inhibiting the nuclear accumulation of MKL1. Several studies have suggested that CCG-1423 interacts not only with MKL1, which has a critical role in the regulation of neuronal morphology, but also with phosphatase and actin regulator 1 (Phactr1), which is localized at synapses. However, the effect of CCG-1423 on neuronal cells, especially on neuronal morphology, remains to be determined. In this study, we focused on the effect of CCG-1423 on axonal elongation, dendritic length, dendritic complexity and dendritic spine morphology. Incubation of cortical neuron cultures with up to 10 μM CCG-1423 for 72 h did not significantly affect cell viability. CCG-1423 inhibited axonal elongation and blocked the increase of dendritic length and complexity, but did not affect dendritic spine morphology. Here, we demonstrated for the first time that CCG-1423 affects neurite elongation, except for dendritic spines, without affecting neuronal cell viability. This study provides a better understanding of the effects of CCG-1423 on neurons, which may be useful for the assessment of the potential clinical application of CCG-1423 and its derivatives. - Highlights: • CCG-1423 does not affect neuronal cell viability. • CCG-1423 inhibits axonal elongation in rat cortical neurons. • CCG-1423 decreases dendritic complexity in a time-dependent manner.},
doi = {10.1016/J.BBRC.2017.08.071},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 492,
place = {United States},
year = {2017},
month = {10}
}