Search

Your search keyword '"Inden, Masatoshi"' showing total 340 results
Start Over Author "Inden, Masatoshi"
340 results on '"Inden, Masatoshi"'

5. Epigenetic alternations in the SYP and DLG4 genes due to low‐level methylmercury exposure during neuronal differentiation in vitro.

Author

Kurita, Hisaka, Masuda, Haruka, Okuda, Ayu, Go, Suzuna, Ohuchi, Kazuki, Yoshioka, Hiroki, Fujimura, Masatake, Hozumi, Isao, and Inden, Masatoshi

Subjects
SCAFFOLD proteins, GENE expression, NEURONAL differentiation, CENTRAL nervous system, FETAL development
Abstract

Methylmercury (MeHg) is an environmental toxin known to damage the central nervous system. When pregnant women ingest seafood, which may contain accumulated MeHg, fetal development may be affected. The embryonic period, a time of major epigenetic change, is susceptible to epigenetic disruptions due to chemical exposure. Therefore, understanding the molecular mechanism underlying MeHg's effects on neuronal development requires consideration of epigenetic factors. In this study, we investigated epigenetic modifications in the synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2–8 of neural differentiation. MeHg exposure significantly reduced the number of spikes observed on day 16 of differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. Additionally, MeHg treatment reduced acetyl histone H3 levels associated with transcriptional activity in the SYP gene while increasing histone H3 lysine 27 tri‐methylation (H3K27me3) levels related to transcriptional repression. Conversely, regarding the DLG4 gene, MeHg exposure increased H3K27me3 levels. Differential changes in DNA methylation (high and low methylation states) were observed in the SYP and DLG4 genes due to MeHg exposure depending on CpG site position. In conclusion, this study suggests that epigenetic changes, particularly histone modifications, contribute to decreased MeHg exposure‐induced SYP and DLG4 expression during neuronal differentiation. Epigenetic modifications in synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes were investigated. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2–8 of neural differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. MeHg exposure increased histone H3 lysine 27 tri‐methylation levels in SYP and DLG4 promoters. In conclusion, epigenetic changes would decrease MeHg exposure‐induced SYP and DLG4 expression during neuronal differentiation. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

28. Stem Cells From Human Exfoliated Deciduous Teeth-Conditioned Medium (SHED-CM) is a Promising Treatment for Amyotrophic Lateral Sclerosis

Author

Ueda, Tomoyuki, Ito, Taisei, Inden, Masatoshi, Kurita, Hisaka, Yamamoto, Akihito, Hozumi, Isao, Ueda, Tomoyuki, Ito, Taisei, Inden, Masatoshi, Kurita, Hisaka, Yamamoto, Akihito, and Hozumi, Isao

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by the loss of upper and lower motor neurons, for which an effective treatment has yet to be developed. Previous reports have shown that excessive oxidative stress, related to mitochondrial dysfunction and the accumulation of misfolding protein, contributes to ALS pathology. In terms of treatment, it remains necessary to identify effective medicines for multiple therapeutic targets and have additive effects against several disorders. In this study, we investigated stem cells from human exfoliated deciduous teeth (SHED), which release many factors, such as neurotrophic factors and cytokines, and are applied to treat neurological diseases. Specifically, we examined whether SHED-conditioned medium (CM), i.e., the serum-free culture supernatant of SHED, reduced mutant SOD1-induced intracellular aggregates and neurotoxicity. We found that SHED-CM significantly suppressed the mutant SOD1-induced intracellular aggregates and neurotoxicity. The neuroprotective effects of SHED-CM are partly related to heat shock protein and the activation of insulin-like growth factor-1 receptor. SHED-CM also had a protective effect on induced pluripotent stem cell-derived motor neurons. Moreover, SHED-CM was effective against not only familial ALS but also sporadic ALS. Overall, these results suggest that SHED-CM could be a promising treatment for slowing the progression of ALS.

Published
2022

38. Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network

Author

Umetsu, Ryogo, primary, Tanaka, Mizuki, additional, Nakayama, Yoko, additional, Kato, Yamato, additional, Ueda, Natsumi, additional, Nishibata, Yuri, additional, Hasegawa, Shiori, additional, Matsumoto, Kiyoka, additional, Takeyama, Noriaki, additional, Iguchi, Kazuhiro, additional, Tanaka, Hiroyuki, additional, Hinoi, Eiichi, additional, Inagaki, Naoki, additional, Inden, Masatoshi, additional, Muto, Yoshinori, additional, and Nakamura, Mitsuhiro, additional

Published
2021
Full Text
View/download PDF

43. A Golgi-targeting fluorescent probe for labile Fe(ii) to reveal an abnormal cellular iron distribution induced by dysfunction of VPS35† †Electronic supplementary information (ESI) available: NMR spectra of the newly synthesized compounds, experimental details and additional data of synthesis, spectroscopic studies, photostability, knockdown/mutation of VPS35 by lentivirus infection, Western blotting, total iron quantification, cytotoxicity assay, and imaging studies. See DOI: 10.1039/c8sc04386h

Author

Hirayama, Tasuku, Inden, Masatoshi, Tsuboi, Hitomi, Niwa, Masato, Uchida, Yasuhiro, Naka, Yuki, Hozumi, Isao, and Nagasawa, Hideko

Subjects
Chemistry
Abstract

Fluctuation of labile Fe(ii) at Golgi apparatus was specifically detected by a new fluorescent probe., Iron is involved in numerous physiologically essential processes in our body. However, excessive iron is a pathogenic factor in neurodegenerative diseases, causing aberrant oxidative stress. Divalent metal transporter 1 (DMT1) acts as a primary transporter of Fe(ii) ions. The intracellular delivery of DMT1 toward the cellular membrane via the trans-Golgi network during the endocytotic process is partially regulated by a retromer-mediated protein-sorting system comprising vacuolar protein-sorting proteins (VPSs). Thus, together with DMT1, the Golgi-apparatus acts as a hub organelle in the delivery system for intracellular Fe(ii) ions. Dysfunction of the VPS-relevant protein sorting system can induce the abnormal delivery of DMT1 toward lysosomes concomitantly with Fe(ii) ions. To explore this issue, we developed a fluorescent probe, Gol-SiRhoNox, for the Golgi-specific detection of Fe(ii) ions by integrating our original N-oxide-based Fe(ii)-specific chemical switch, a new Golgi-localizable chemical motif, and polarity-sensitive fluorogenic scaffold. Our synchronous imaging study using Gol-SiRhoNox and LysoRhoNox, a previously developed fluorescent probe for lysosomal Fe(ii), revealed that the intracellular distribution balance of Fe(ii) ions between the Golgi apparatus and lysosomes is normally Golgi-dominant, whereas the lysosome-specific elevation of Fe(ii) ions was observed in cells with induced dysfunction of VPS35, a member of the retromer complex. Treatment of cells with dysfunctional VPS35 with R55, a molecular chaperone, resulted in the restoration of the subcellular distribution of Fe(ii) ions to the Golgi-dominant state. These results indicate that the impairment of the DMT1 traffic machinery affects subcellular iron homeostasis, promoting Fe(ii) leakage at the Golgi and lysosomal accumulation of Fe(ii) through missorting of DMT1.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results