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Start Over Author "Toyoshima A" Journal proceedings of the national academy of sciences of the united states of america
141 results on '"Toyoshima A"'

1. Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation

Author

Ma, Min, Ren, Qian, Yang, Jun, Zhang, Kai, Xiong, Zhongwei, Ishima, Tamaki, Pu, Yaoyu, Hwang, Sung Hee, Toyoshima, Manabu, Iwayama, Yoshimi, Hisano, Yasuko, Yoshikawa, Takeo, Hammock, Bruce D, and Hashimoto, Kenji

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Intellectual and Developmental Disabilities (IDD), Neurosciences, Pediatric, Genetics, Stem Cell Research, Mental Illness, Brain Disorders, Serious Mental Illness, Women's Health, Mental Health, Autism, Behavioral and Social Science, Schizophrenia, Prevention, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Mental health, Reproductive health and childbirth, Animals, Epoxide Hydrolases, Female, Gene Expression Regulation, Enzymologic, Maternal Exposure, Mice, Neurodevelopmental Disorders, Phenylurea Compounds, Piperidines, Prefrontal Cortex, Pregnancy, Prenatal Exposure Delayed Effects, epoxy fatty acid, ER stress, iPSCs, maternal infection, prevention
Abstract

Maternal infection during pregnancy increases risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) in offspring. In rodents, maternal immune activation (MIA) yields offspring with schizophrenia- and ASD-like behavioral abnormalities. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with neurodevelopmental disorders. Here we found higher levels of sEH in the prefrontal cortex (PFC) of juvenile offspring after MIA. Oxylipin analysis showed decreased levels of epoxy fatty acids in the PFC of juvenile offspring after MIA, supporting increased activity of sEH in the PFC of juvenile offspring. Furthermore, expression of sEH (or EPHX2) mRNA in induced pluripotent stem cell-derived neurospheres from schizophrenia patients with the 22q11.2 deletion was higher than that of healthy controls. Moreover, the expression of EPHX2 mRNA in postmortem brain samples (Brodmann area 9 and 40) from ASD patients was higher than that of controls. Treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, in juvenile offspring from prenatal day (P) 28 to P56 could prevent cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial PFC of adult offspring after MIA. In addition, dosing of TPPU to pregnant mothers from E5 to P21 could prevent cognitive deficits, and social interaction deficits and PV immunoreactivity in the medial prefrontal cortex of juvenile offspring after MIA. These findings suggest that increased activity of sEH in the PFC plays a key role in the etiology of neurodevelopmental disorders in offspring after MIA. Therefore, sEH represents a promising prophylactic or therapeutic target for neurodevelopmental disorders in offspring after MIA.

Published
2019

9. Requirement of zinc transporter ZIP10 for epidermal development : Implication of the ZIP10–p63 axis in epithelial homeostasis

Author

Bin, Bum-Ho, Bhin, Jinhyuk, Takaishi, Mikiro, Toyoshima, Koh-ei, Kawamata, Saeko, Ito, Kana, Hara, Takafumi, Watanabe, Takashi, Irié, Tarou, Takagishi, Teruhisa, Lee, Su-Hyon, Jung, Haeng-Sun, Rho, Sangchul, Seo, Juyeon, Choi, Dong-Hwa, Hwang, Daehee, Koseki, Haruhiko, Ohara, Osamu, Sano, Shigetoshi, Tsuji, Takashi, Mishima, Kenji, and Fukada, Toshiyuki

Published
2017

16. Neuronal sensorimotor integration guiding salt concentration navigation in Caenorhabditis elegans.

Author

Ayaka Matsumoto, Yu Toyoshima, Chenqi Zhang, Akihiro Isozaki, Keisuke Goda, and Yuichi Iino

Subjects
*SENSORIMOTOR integration, *CAENORHABDITIS elegans, *MOTOR neurons, *MICROFLUIDIC devices, *BEHAVIORAL assessment
Abstract

Animals navigate their environment by manipulating their movements and adjusting their trajectory which requires a sophisticated integration of sensory data with their current motor status. Here, we utilize the nematode Caenorhabditis elegans to explore the neural mechanisms of processing the sensory and motor information for navigation. We developed a microfluidic device which allows animals to freely move their heads while receiving temporal NaCl stimuli. We found that C. elegans regulates neck bending direction in response to temporal NaCl concentration changes in a way which is consistent with a C. elegans' navigational strategy which regulates traveling direction toward preferred NaCl concentrations. Our analysis also revealed that the activity of a neck motor neuron is significantly correlated with neck bending and activated by the decrease in NaCl concentration in a phase-dependent manner. By combining the analysis of behavioral and neural response to NaCl stimuli and optogenetic perturbation experiments, we revealed that NaCl decrease during ventral bending activates the neck motor neuron which counteracts ipsilateral bending. Simulations further suggest that this phase-dependent response of neck motor neurons can facilitate curving toward preferred salt concentrations. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome

Author

Arima, Kazuhiko, Kinoshita, Akira, Mishima, Hiroyuki, Kanazawa, Nobuo, Kaneko, Takeumi, Mizushima, Tsunehiro, Ichinose, Kunihiro, Nakamura, Hideki, Tsujino, Akira, Kawakami, Atsushi, Matsunaka, Masahiro, Kasagi, Shimpei, Kawano, Seiji, Kumagai, Shunichi, Ohmura, Koichiro, Mimori, Tsuneyo, Hirano, Makito, Ueno, Satoshi, Tanaka, Keiko, Tanaka, Masami, Toyoshima, Itaru, Sugino, Hirotoshi, Yamakawa, Akio, Tanaka, Keiji, Niikawa, Norio, Furukawa, Fukumi, Murata, Shigeo, Eguchi, Katsumi, Ida, Hiroaki, and Yoshiura, Koh-ichiro

Published
2011

23. Cryoelectron microscopy of Na

Author

Ryuta, Kanai, Flemming, Cornelius, Bente, Vilsen, and Chikashi, Toyoshima

Subjects
Cardiac Glycosides, Adenosine Triphosphate, Cardiotonic Agents, Protein Domains, Cations, Cryoelectron Microscopy, Etiocholanolone, Sodium, Magnesium, Sodium-Potassium-Exchanging ATPase, Ouabain
Abstract

Cryoelectron microscopy (cryo-EM) was applied to Na+,K+-ATPase (NKA) to determine the structures of two E2P states, one (E2PATP) formed by ATP and Mg2+ in the forward reaction, and the other (E2PPi) formed by inorganic phosphate (Pi) and Mg2+ in the backward reaction, with and without ouabain or istaroxime, representatives of classical and new-generation cardiotonic steroids (CTSs). These two E2P states exhibit different biochemical properties. In particular, K+-sensitive acceleration of the dephosphorylation reaction is not observed with E2PPi, attributed to the presence of a Mg2+ ion in the transmembrane cation binding sites. The cryo-EM structures of NKA demonstrate that the two E2P structures are nearly identical but Mg2+ in the transmembrane binding cavity is identified only in E2PPi, corroborating the idea that it should be denoted as E2PPi·Mg2+. We can now explain why the absence of transmembrane Mg2+ in E2PATP confers the K+ sensitivity in dephosphorylation. In addition, we show that ATP bridges the actuator (A) and nucleotide binding (N) domains, stabilizing the E2PATP state; CTS binding causes hardly any changes in the structure of NKA, both in E2PATP and E2PPi·Mg2+, indicating that the binding mechanism is conformational selection; and istaroxime binds to NKA, extending its aminoalkyloxime group deep into the cation binding site. This orientation is upside down compared to that of classical CTSs with respect to the steroid ring. Notably, mobile parts of NKA are resolved substantially better in the electron microscopy (EM) maps than in previous X-ray structures, including sugars sticking out from the β-subunit and many phospholipid molecules.

Published
2022

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