研究等業績 - 原著論文 - 安田　大恭

Lysophosphatidic acid-induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Daisuke Yasuda, Daiki Kobayashi, Noriyuki Akahoshi, Takayo Ohto-Nakanishi, Kazuaki Yoshioka, Yoh Takuwa, Seiya Mizuno, Satoru Takahashi, and Satoshi Ishii

J. Clin. Invest.   ( 129 ) 4332 - 4349   2019年10月  [査読有り]

研究論文（学術雑誌）   国内共著

The Gα12/13-coupled receptor, LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity

Keisuke Yanagida, Hidemitsu Igarashi, Daisuke Yasuda, Daiki Kobayashi, Takayo Ohto-Nakanishi, Noriyuki Akahoshi, Atsushi Sekiba, Tsudoi Toyoda, Tomoko Ishijima, Yuji Nakai, Nobuhiro Shojima, Naoto Kubota, Keiko Abe, Takashi Kadowaki, Satoshi Ishii, and Takao Shimizu

JCI Insight   ( 3 ) e97293   2018年12月  [査読有り]

研究論文（学術雑誌）   国内共著

Identification of optineurin as an interleukin-1 receptor-associated kinase 1-binding protein and its role in regulation of MyD88-dependent signaling

Mitsuyoshi Tanishima, Shigeo Takashima, Arata Honda, Daisuke Yasuda, Takashi Tanikawa, Satoshi Ishii, and Takashi MaruYama

J. Biol. Chem.   ( 292 ) 17250 - 17257   2017年10月  [査読有り]

研究論文（学術雑誌）   国内共著

Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact

Kazuhiro Takara, Daisuke Eino, Koji Ando, Daisuke Yasuda, Hisamichi Naito, Yohei Tsukada, Tomohiro Iba, Taku Wakabayashi, Fumitaka Muramatsu, Hiroyasu Kidoya, Shigetomo Fukuhara, Naoki Mochizuki, Satoshi Ishii, Haruhiko Kishima, and Nobuyuki Takakura

Cell Rep.   20   2072 - 2086   2017年08月  [査読有り]

研究論文（学術雑誌）   国内共著

薬理学的シャペロン―小胞体蓄積GPCR を形質膜へ発現させる特異的リガンド

安田大恭, 中村元直

医学のあゆみ   256   385 - 392   2016年01月  [招待有り]

研究論文（学術雑誌）   国内共著

The lysophosphatidic acid receptor LPA4 regulates hematopoiesis-supporting activity of bone marrow stromal cells

Hidemitsu Igarashi, Noriyuki Akahoshi, Takayo Ohto-Nakanishi, Daisuke Yasuda, and Satoshi Ishii

Sci. Rep.   5   11410   2015年06月  [査読有り]

研究論文（学術雑誌）   国内共著

The atypical N-glycosylation motif, Asn-Cys-Cys, in human GPR109A is required for normal cell surface expression and intracellular signaling

Daisuke Yasuda, Yuki Imura, Satoshi Ishii, Takao Shimizu, Motonao Nakamura

The FASEB Journal     2015年02月  [査読有り]

研究論文（学術雑誌）   国内共著

Amino acid residues of G-protein-coupled receptors critical for endoplasmic reticulum export and trafficking

Motonao Nakamura, Daisuke Yasuda, Nobuaki Hirota, Teruyasu Yamamoto, Satoshi Yamaguchi, Takao Shimizu and Teruyuki Nagamune

Methods in Enzymology     2013年01月  [査読有り]  [招待有り]

研究論文（学術雑誌）   国内共著

Specific ligands as pharmacological chaperons: The transport of misfolded G-protein coupled receptors to the cell surface

Motonao Nakamura, Daisuke Yasuda, Nobuaki Hirota, and Takao Shimizu

IUBMB Life     2010年05月  [査読有り]  [招待有り]

研究論文（学術雑誌）   国内共著

Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor

Nobuaki Hirota, Daisuke Yasuda, Tomomi Hashidate, Teruyasu Yamamoto, Satoshi Yamaguchi, Teruyuki Nagamune, Takahide Nagase, Takao Shimizu and Motonao Nakamura

Journal of Biological Chemistry     2010年02月  [査読有り]

研究論文（学術雑誌）   国内共著

Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides

Hisashi Matsuda, Kiyofumi Ninomiya, Toshio Morikawa, Daisuke Yasuda, Itadaki Yamaguchi and Masayuki Yoshikawa

Bioorganic & Medicinal Chemistry     2009年08月  [査読有り]

研究論文（学術雑誌）   国内共著

Helix 8 of leukotriene B4 type-2 receptor is required for the folding to pass the quality control in the endoplasmic reticulum

Daisuke Yasuda , Toshiaki Okuno, Takehiko Yokomizo, Tetsuya Hori, Nobuaki Hirota, Tomomi Hashidate, Masashi Miyano, Takao Shimizu and Motonao Nakamura

FASEB Journal     2009年05月  [査読有り]

研究論文（学術雑誌）   国内共著

特異的リガンドによる小胞体蓄積GPCRの細胞膜への搬出

安田大恭, 中村元直

生化学     2013年11月  [査読有り]  [招待有り]

研究論文（学術雑誌）   国内共著

Medicinal Foodstuffs. XXXIV. Structures of New Prenylchalcones and Prenylflavanones with TNF-alfa and Aminopeptidase N Inhibitory Activities from Boesenbergia rotunda

Toshio Morikawa, Kanako Funakoshi, Kiyofumi Ninomiya, Daisuke Yasuda, Katsutoshi Miyagawa, Hisashi Matsuda, and Masayuki Yoshikawa

Chem. Pharm. Bull.   56   956 - 962   2008年04月  [査読有り]

研究論文（学術雑誌）   国内共著

サザンブロッティングとウェスタンブロッティング

石井聡, 安田大恭

呼吸     2013年09月  [査読有り]  [招待有り]

研究論文（学術雑誌）   国内共著

ロイコトリエンの多様な疾患へのかかわり—受容体改変マウスの解析から

安田大恭, 石井聡

実験医学（増刊）     2010年12月  [査読有り]  [招待有り]

研究論文（学術雑誌）   国内共著

Inverse agonism of lysophospholipids with cationic head groups at Gi-coupled receptor GPR82

Yasuda D.

European Journal of Pharmacology ( European Journal of Pharmacology )  954   175893 - 175893   2023年09月  [査読有り]

研究論文（学術雑誌）  

GPR82 is an orphan G protein-coupled receptor (GPCR) that has been implicated in lipid storage in mouse adipocytes. However, the intracellular signaling as well as the specific ligands of GPR82 remain unknown. GPR82 is closely related to GPR34, a GPCR for the bioactive lipid molecule lysophosphatidylserine. In this study, we screened a lipid library using GPR82-transfected cells to search for ligands that act on GPR82. By measuring cyclic adenosine monophosphate levels, we found that GPR82 is an apparently constitutively active GPCR that leads to Gi protein activation. In addition, edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine), an artificial lysophospholipid with a cationic head group that exerts antitumor activity, inhibited the Gi protein activation by GPR82. Two endogenous lysophospholipids with cationic head groups, lysophosphatidylcholine (1-oleoyl-sn-glycero-3-phosphocholine) and lysophosphatidylethanolamine (1-oleoyl-sn-glycero-3-phosphoethanolamine), also exhibited GPR82 inhibitory activity, albeit weaker than edelfosine. Förster resonance energy transfer imaging analysis consistently demonstrated that Gi protein-coupled GPR82 has an apparent constitutive activity that is edelfosine-sensitive. Consistent data were obtained from GPR82-mediated binding analysis of guanosine-5'-O-(3-thiotriphosphate) to cell membranes. Furthermore, in GPR82-transfected cells, edelfosine inhibited insulin-induced extracellular signal-regulated kinase activation, like compounds that function as inverse agonists at other GPCRs. Therefore, edelfosine is likely to act as an inverse agonist of GPR82. Finally, GPR82 expression inhibited adipocyte lipolysis, which was abrogated by edelfosine. Our findings suggested that the cationic lysophospholipids edelfosine, lysophosphatidylcholine and lysophosphatidylethanolamine are novel inverse agonists for Gi-coupled GPR82, which is apparently constitutively active, and has the potential to exert lipolytic effects through GPR82.

DOI PubMed

Inverse agonism of lysophospholipids with cationic head groups at Gi-coupled receptor GPR82

Yasuda D.

European Journal of Pharmacology ( European Journal of Pharmacology )  954   175893 - 175893   2023年09月  [査読有り]

研究論文（学術雑誌）  

GPR82 is an orphan G protein-coupled receptor (GPCR) that has been implicated in lipid storage in mouse adipocytes. However, the intracellular signaling as well as the specific ligands of GPR82 remain unknown. GPR82 is closely related to GPR34, a GPCR for the bioactive lipid molecule lysophosphatidylserine. In this study, we screened a lipid library using GPR82-transfected cells to search for ligands that act on GPR82. By measuring cyclic adenosine monophosphate levels, we found that GPR82 is an apparently constitutively active GPCR that leads to Gi protein activation. In addition, edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine), an artificial lysophospholipid with a cationic head group that exerts antitumor activity, inhibited the Gi protein activation by GPR82. Two endogenous lysophospholipids with cationic head groups, lysophosphatidylcholine (1-oleoyl-sn-glycero-3-phosphocholine) and lysophosphatidylethanolamine (1-oleoyl-sn-glycero-3-phosphoethanolamine), also exhibited GPR82 inhibitory activity, albeit weaker than edelfosine. Förster resonance energy transfer imaging analysis consistently demonstrated that Gi protein-coupled GPR82 has an apparent constitutive activity that is edelfosine-sensitive. Consistent data were obtained from GPR82-mediated binding analysis of guanosine-5'-O-(3-thiotriphosphate) to cell membranes. Furthermore, in GPR82-transfected cells, edelfosine inhibited insulin-induced extracellular signal-regulated kinase activation, like compounds that function as inverse agonists at other GPCRs. Therefore, edelfosine is likely to act as an inverse agonist of GPR82. Finally, GPR82 expression inhibited adipocyte lipolysis, which was abrogated by edelfosine. Our findings suggested that the cationic lysophospholipids edelfosine, lysophosphatidylcholine and lysophosphatidylethanolamine are novel inverse agonists for Gi-coupled GPR82, which is apparently constitutively active, and has the potential to exert lipolytic effects through GPR82.

DOI PubMed

Cell-trafficking impairment in disease-associated LPA6 missense mutants and a potential pharmacoperone therapy for autosomal recessive woolly hair/hypotrichosis

Yanagida K.

Human molecular genetics ( Human molecular genetics )  32 ( 5 ) 825 - 834   2023年02月

研究論文（学術雑誌）  

Abstract

In human autosomal recessive woolly hair/hypotrichosis (ARWH/HT), many mutations have been identified in a gene encoding LPA6, a G protein-coupled receptor (GPCR) for lysophosphatidic acid (LPA). However, information regarding the effects of such mutations on receptor function is limited. In this study, we examined functional impacts of selected amino acid changes in LPA6 identified in ARWH/HT patients. In our exogenous expression experiments, all mutants except S3T failed to respond to LPA, indicating that they are loss-of-function mutants. Among the nine mutants, five (D63V, G146R, N246D, L277P, and C278Y) displayed impaired expression at the cell surface due to endoplasmic reticulum (ER) retention, indicating that these mutants are trafficking-defective, as reported in other disease-associated GPCRs. Notably, alkyl-OMPT, a potent synthetic agonist for LPA6 restored the defective cell surface expression of two of the ER-retained mutants, D63V and N246D, possibly by its chaperoning function that allows them to escape intracellular retention as well as proteasomal degradation. Furthermore, the alkyl-OMPT-rescued N246D mutant was shown be functional. Our findings encourage future application of pharmacoperone therapy for ARWH/HT patients with specific LPA6 mutations.

DOI

Protective effects of amide constituents from the fruit of Piper chaba on d-galactosamine/TNF-α-induced cell death in mouse hepatocytes

Hisashi Matsuda, Kiyofumi Ninomiya, Toshio Morikawa, Daisuke Yasuda, Itadaki Yamaguchi, and Masayuki Yoshikawa

Bioorganic & Medicinal Chemistry Letters     2008年01月  [査読有り]

研究論文（学術雑誌）   国内共著