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Article: N

Karanjule, Narayan / Hayashi, Noriyuki / Suzuki, Sayaka / Tsuda, Toshifumi / Tokumaru, Eri / Tanaka, Kyosuke / Kimoto, Hiroko / Domon, Yuki / Takahashi, Sakiko / Kubota, Kazufumi / Kitano, Yutaka / Yokoyama, Tomihisa / Koishi, Ryuta / Fujiwara, Chie / Inaba, Shinichi / Asano, Daigo / Sakakura, Tomoko / Takasuna, Kiyoshi / Shinozuka, Tsuyoshi

ACS medicinal chemistry letters

2023 Volume 14, Issue 6, Page(s) 788–793

Abstract: A novel class of potent ... ...

Abstract	A novel class of potent Na
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/acsmedchemlett.3c00079
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Article ; Online: N

Kida, Tatsuya / Takahashi, Nobuaki / Mori, Masayuki X / Sun, Jiacheng H / Oota, Hideto / Nishino, Kosuke / Okauchi, Takashi / Ochi, Yuta / Kano, Daisuke / Tateishi, Ukihide / Watanabe, Yasuyoshi / Cui, Yilong / Mori, Yasuo / Doi, Hisashi

RSC medicinal chemistry

2022 Volume 13, Issue 10, Page(s) 1197–1204

Abstract: Transient receptor potential cation channel subfamily V member 1 (TRPV1)-targeted compounds were synthesized by modifying the structure of SB366791, a pharmaceutically representative TRPV1 antagonist. To avoid amide-iminol tautomerization, structurally ... ...

Abstract	Transient receptor potential cation channel subfamily V member 1 (TRPV1)-targeted compounds were synthesized by modifying the structure of SB366791, a pharmaceutically representative TRPV1 antagonist. To avoid amide-iminol tautomerization, structurally supported
Language	English
Publishing date	2022-09-06
Publishing country	England
Document type	Journal Article
ISSN	2632-8682
ISSN (online)	2632-8682
DOI	10.1039/d2md00158f
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Article ; Online: Dissolved N

Nishina, Kazuya / Melling, Lulie / Toyoda, Sakae / Itoh, Masayuki / Terajima, Kotaro / Waili, Joseph W B / Wong, Guan X / Kiew, Frankie / Aeries, Edward B / Hirata, Ryuichi / Takahashi, Yoshiyuki / Onodera, Takashi

The Science of the total environment

2023 Volume 872, Page(s) 162062

Abstract: ... ecosystems have a unique water management system that lowers the water table and, thus, may yield indirect N ...

Abstract	Oil palm plantations in Southeast Asia are the largest supplier of palm oil products and have been rapidly expanding in the last three decades even in peat-swamp areas. Oil palm plantations on peat ecosystems have a unique water management system that lowers the water table and, thus, may yield indirect N
Language	English
Publishing date	2023-02-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2023.162062
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Zs.A 949: Show issues

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Article ; Online: Synthesis of a fluorescent probe for measuring the activity of endo-β-N-acetylglucosaminidases recognizing hybrid-type N-glycans.

Ishii, Nozomi / Inoue, Shusei / Sano, Kanae / Takahashi, Satoshi / Matsuo, Ichiro

Bioorganic & medicinal chemistry

2024 Volume 100, Page(s) 117612

Abstract: ... of endo-β-N-acetylglucosaminidases (ENGases) interacting with hybrid-type N-glycans. This was achieved ... of the resulting nonasaccharide derivative were removed, and the derivative was labeled with an N ... could also assist in the search for novel ENGases that are specific to hybrid-type N-glycans. ...

Abstract	A fluorescence-quenching-based assay system was constructed to determine the hydrolytic activity of endo-β-N-acetylglucosaminidases (ENGases) interacting with hybrid-type N-glycans. This was achieved using a dual-labeled fluorescent probe with a nonasaccharide structure. We produced the nonasaccharide skeleton by the stepwise glycosylation of the galactose residue on a galactosyl chitobiose derivative. Next, we introduced azido and acetoxy groups into the nonasaccharide derivative in a stepwise manner, which led to stereochemistry inversion at both the C-4 and C-2 hydroxy groups on its galactose residue. The protecting groups of the resulting nonasaccharide derivative were removed, and the derivative was labeled with an N-methylanthraniloyl group to obtain a reporter dye and a 2,4-dinitrophenyl group as a quenching molecule to obtain target probe 1. The use of this probe along with a microplate reader enabled a facile evaluation of the hydrolytic activities of ENGases Endo-H, Endo-M, Endo-F3, Endo-S, and Endo-CC. Furthermore, this probe could also assist in the search for novel ENGases that are specific to hybrid-type N-glycans.
MeSH term(s)	Fluorescent Dyes/chemistry ; Acetylglucosaminidase/chemistry ; Galactose ; Polysaccharides/chemistry ; Glycosylation ; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/metabolism
Chemical Substances	Fluorescent Dyes ; Acetylglucosaminidase (EC 3.2.1.52) ; Galactose (X2RN3Q8DNE) ; Polysaccharides ; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase (EC 3.2.1.96)
Language	English
Publishing date	2024-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2024.117612
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Zs.A 3815: Show issues

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Article ; Online: N-glycan on N262 of FGFR3 regulates the intracellular localization and phosphorylation of the receptor.

Hashimoto, Ukichiro / Fujitani, Naoki / Uehara, Yasuaki / Okamoto, Hiromi / Saitou, Atsushi / Ito, Fumie / Ariki, Shigeru / Shiratsuchi, Akiko / Hasegawa, Yoshihiro / Takahashi, Motoko

Biochimica et biophysica acta. General subjects

2024 Volume 1868, Issue 4, Page(s) 130565

Abstract: N-glycosylation and proper processing of N-glycans are required for the function ... cell proliferation. Human FGFR3 contains six potential N-glycosylation sites, however, the roles of glycosylation ... have not been elucidated. The site-specific profiles of N-glycans of the FGFR3 extracellular domain ...

Abstract	N-glycosylation and proper processing of N-glycans are required for the function of membrane proteins including cell surface receptors. Fibroblast growth factor receptor (FGFR) is involved in a wide variety of biological processes including embryonic development, osteogenesis, angiogenesis, and cell proliferation. Human FGFR3 contains six potential N-glycosylation sites, however, the roles of glycosylation have not been elucidated. The site-specific profiles of N-glycans of the FGFR3 extracellular domain expressed and secreted by CHO-K1 cells were examined, and glycan occupancies and structures of four sites were determined. The results indicated that most sites were fully occupied by glycans, and the dominant populations were the complex type. By examining single N-glycan deletion mutants of FGFR3, it was found that N262Q mutation significantly increased the population with oligomannose-type N-glycans, which was localized in the endoplasmic reticulum. Protein stability assay suggested that fraction with oligomannose-type N-glycans in the N262Q mutant is more stable than those in the wild type and other mutants. Furthermore, it was found that ligand-independent phosphorylation was significantly upregulated in N262Q mutants with complex type N-glycans. The findings suggest that N-glycans on N262 of FGFR3 affect the intracellular localization and phosphorylation status of the receptor.
MeSH term(s)	Cricetinae ; Animals ; Humans ; Phosphorylation ; Glycosylation ; CHO Cells ; Cricetulus ; Polysaccharides/metabolism ; Biological Phenomena ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptor, Fibroblast Growth Factor, Type 3/metabolism
Chemical Substances	Polysaccharides ; FGFR3 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
Language	English
Publishing date	2024-01-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2024.130565
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Article ; Online: N-glycosylation regulates MET processing and signaling.

Saitou, Atsushi / Hasegawa, Yoshihiro / Fujitani, Naoki / Ariki, Shigeru / Uehara, Yasuaki / Hashimoto, Ukichiro / Saito, Atsushi / Kuronuma, Koji / Matsumoto, Kunio / Chiba, Hirofumi / Takahashi, Motoko

Cancer science

2022 Volume 113, Issue 4, Page(s) 1292–1304

Abstract: ... potential N-glycosylation sites, but the site-specific roles of these N-glycans have not been elucidated ... We report herein that these N-glycans regulate the proteolytic processing of MET and HGF-induced MET ... signaling, and that this regulation is site specific. Inhibitors of N-glycosylation were found to suppress ...

Abstract	MET, the receptor for the hepatocyte growth factor (HGF), is strongly associated with resistance to tyrosine kinase inhibitors, key drugs that are used in the therapy of non-small cell lung cancer. MET contains 11 potential N-glycosylation sites, but the site-specific roles of these N-glycans have not been elucidated. We report herein that these N-glycans regulate the proteolytic processing of MET and HGF-induced MET signaling, and that this regulation is site specific. Inhibitors of N-glycosylation were found to suppress the processing and trafficking of endogenous MET in H1975 and EBC-1 lung cancer cells and exogenous MET in CHO-K1 cells. We purified the recombinant extracellular domain of human MET and determined the site-specific N-glycan structures and occupancy using mass spectrometry. The results indicated that most sites were fully glycosylated and that the dominant population was the complex type. To examine the effects of the deletion of N-glycans of MET, we prepared endogenous MET knockout Flp-In CHO cells and transfected them with a series of N-glycan-deletion mutants of MET. The results showed that several N-glycans are implicated in the processing of MET. The findings also suggested that the N-glycans of the SEMA domain of MET positively regulate HGF signaling, and the N-glycans of the region other than the SEMA domain negatively regulate HGF signaling. Processing, cell surface expression, and signaling were significantly suppressed in the case of the all-N-glycan-deletion mutant. The overall findings suggest that N-glycans of MET affect the status and the function of the receptor in a site-specific manner.
MeSH term(s)	Animals ; Carcinoma, Non-Small-Cell Lung ; Cricetinae ; Cricetulus ; Glycosylation ; Hepatocyte Growth Factor/metabolism ; Humans ; Lung Neoplasms/drug therapy ; Proto-Oncogene Proteins c-met
Chemical Substances	Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2022-02-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.15278
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Article ; Online: Seroprevalence of severe acute respiratory syndrome coronavirus 2 N antibodies between December 2021 and march 2023 in Japan.

Yamayoshi, Seiya / Nagai, Etsuko / Mitamura, Keiko / Hagihara, Masao / Kobayashi, Ryo / Takahashi, Satoshi / Shibata, Akimichi / Uwamino, Yoshifumi / Hasegawa, Naoki / Iqbal, Asef / Kamimaki, Isamu / Iwatsuki-Horimoto, Kiyoko / Nagamura-Inoue, Tokiko / Kawaoka, Yoshihiro

Epidemiology and infection

2024 Volume 152, Page(s) e24

Abstract: ... the emergence of the omicron variants, the seroprevalence of antibodies against the N protein elicited by SARS ... against N was conducted between December 2021 and March 2023 in Japan. In total, 7604 and 3354 residual ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 in China and rapidly spread worldwide, leading to a pandemic. The threat of SARS-CoV-2 is subsiding as most people have acquired sufficient antibodies through vaccination and/or infection to prevent severe COVID-19. After the emergence of the omicron variants, the seroprevalence of antibodies against the N protein elicited by SARS-CoV-2 infection ranged from 44.4% to 80.2% in countries other than Japan. Here, we assessed the seroprevalence in Japan before and after the appearance of omicron variants. Serosurveillance of antibodies against N was conducted between December 2021 and March 2023 in Japan. In total, 7604 and 3354 residual serum or plasma samples were collected in the Tokyo metropolitan area and Sapporo, respectively. We found that the seroprevalence in representative regions of Japan increased approximately 3% to 23% after the emergence of the omicron variants. We also found higher seroprevalence among the young compared with the elderly. Our findings indicate that unlike other countries, most of the Japanese population has not been infected, raising the possibility of future SARS-CoV-2 epidemics in Japan.
MeSH term(s)	Aged ; Humans ; Japan/epidemiology ; SARS-CoV-2 ; Seroepidemiologic Studies ; COVID-19/epidemiology ; Antibodies, Viral ; Pandemics
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	632982-2
ISSN	1469-4409 ; 0950-2688
ISSN (online)	1469-4409
ISSN	0950-2688
DOI	10.1017/S0950268824000141
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Article ; Online: Synthesis of a Stable N-Hetero-Rh

Takahashi, Shintaro / Nakaya, Kazuki / Frutos, María / Baceiredo, Antoine / Saffon-Merceron, Nathalie / Massou, Stéphane / Nakata, Norio / Hashizume, Daisuke / Branchadell, Vicenç / Kato, Tsuyoshi

Angewandte Chemie (International ed. in English)

2020 Volume 59, Issue 37, Page(s) 15937–15941

Abstract: A novel N-hetero-Rh ...

Abstract	A novel N-hetero-Rh
Language	English
Publishing date	2020-07-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202006088
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Article ; Online: N-acetylcysteine attenuates PGE

Nakamura, Koichi / Minamikawa, Hajime / Takahashi, Shizuka / Yoshimura, Yoshitaka / Yawaka, Yasutaka

Dental materials journal

2021 Volume 40, Issue 3, Page(s) 808–812

Abstract: This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine ...

Abstract	This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine osteoblastic cells cultured on the 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate (4-META/MMA)-based resin. Superbond C&B (SB) was used as the 4-META/MMA-based resin and placed in a 48-well cell culture plate. The cells were cultured in αMEM (control) as well as on SB and SB in αMEM with NAC (SB+NAC). They were examined using the WST-1 proliferation assay, real-time PCR, enzyme-linked immunosorbent assay (ELISA), intracellular reactive oxygen species (ROS) measurements, and cellular glutathione (GSH) detection. COX-2 and IL-6 gene expressions were upregulated in SB; however, they were suppressed by NAC. Furthermore, PGE
MeSH term(s)	Acetylcysteine/pharmacology ; Animals ; Cells, Cultured ; Dinoprostone ; Methacrylates ; Mice ; Reactive Oxygen Species
Chemical Substances	Methacrylates ; Reactive Oxygen Species ; 4-methacryloxyethyltrimellitic acid anhydride (70293-55-9) ; Dinoprostone (K7Q1JQR04M) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2021-03-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	605650-7
ISSN	1881-1361 ; 0287-4547
ISSN (online)	1881-1361
ISSN	0287-4547
DOI	10.4012/dmj.2020-275
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Zs.B 2687: Show issues

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Article ; Online: N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) has potent anti-fibrotic and anti-inflammatory activity in a fibrotic kidney model: is it an old uremic toxin?

Yoshimura, Norito / Yamada, Katsutoshi / Ono, Takashi / Notoya, Mitsuru / Yukioka, Hideo / Takahashi, Rina / Wakino, Shu / Kanda, Takeshi / Itoh, Hiroshi

Clinical and experimental nephrology

2023 Volume 27, Issue 11, Page(s) 901–911

Abstract: ... metabolites, such as N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) and N-methyl-4-pyridone-5-carboxamide (N ... and Western blot analysis were conducted. N-Me-2PY was orally administered to a ligated murine kidney ... fibrosis model (UUO) to evaluate its anti-fibrotic and toxic effects on the body.: Results: N-Me-2PY, N ...

Abstract	Background: Uremic toxins accumulate in renal tissues and cells due to chronic kidney disease (CKD). Abnormalities in nicotinamide adenine dinucleotide (NAD +) metabolism lead to the progression of CKD. NAD + metabolites, such as N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) and N-methyl-4-pyridone-5-carboxamide (N-Me-4PY), have been recognized as uremic toxins. However, no reports have validated whether they are actually harmful to the body. Therefore, we focused on the structural similarity of these metabolites to the anti-fibrotic drug pirfenidone and evaluated their effects on renal fibrosis. Methods: Each NAD + metabolite was treated with TGFβ1 to kidney fibroblasts or tubular epithelial cells, and quantitative RT-PCR and Western blot analysis were conducted. N-Me-2PY was orally administered to a ligated murine kidney fibrosis model (UUO) to evaluate its anti-fibrotic and toxic effects on the body. Results: N-Me-2PY, N-Me-4PY, and nicotinamide N-oxide (NNO) inhibited TGFβ1-induced fibrosis and inflammatory gene expression in kidney fibroblasts. N-Me-2PY strongly suppressed the expression of types I and III collagen, αSMA, and IL-6. N-Me-2PY also suppressed TGFβ1-induced type I collagen and IL-6 expression in renal tubular epithelial cells. No toxic effect was observed with N-Me-2PY treatment, while attenuating renal fibrosis and tubular dilation in UUO mice. Suppression of various fibrosis- and inflammation-related genes was also observed. N-Me-2PY did not inhibit TGFβ1-induced Smad3 phosphorylation but inhibited Akt phosphorylation, suggesting that N-Me-2PY exerts anti-fibrotic and anti-inflammatory effects through Akt inhibition, similar to pirfenidone. Conclusions: NAD + metabolites, such as N-Me-2PY, are not uremic toxins but are potential therapeutic agents that have anti-fibrotic effects in CKD.
MeSH term(s)	Mice ; Animals ; NAD/metabolism ; Uremic Toxins ; Proto-Oncogene Proteins c-akt ; Interleukin-6 ; Kidney/metabolism ; Renal Insufficiency, Chronic/drug therapy ; Anti-Inflammatory Agents/pharmacology ; Fibrosis ; Ureteral Obstruction/complications ; Ureteral Obstruction/drug therapy
Chemical Substances	NAD (0U46U6E8UK) ; Uremic Toxins ; N-methyl-2-pyridone-5-carboxamide ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Interleukin-6 ; Anti-Inflammatory Agents
Language	English
Publishing date	2023-07-25
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-023-02379-1
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