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著作: Natsumi Doi/Hiro Togari/Kenji Minagi/Yuji Iwaoka/[田井 章博]/Koichi Nakaoji/Kazuhiko Hamada/Masaaki Tatsuka/2-O-Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage-induced abnormal spindle orientations/[Journal of Cellular Biochemistry]

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EID
375817
EOID
1008895
Map
0
LastModified
2021年7月5日(月) 19:40:27
Operator
大家 隆弘
Avail
TRUE
Censor
0
Owner
田井 章博
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨 研究
共著種別 推奨 国内共著(徳島大学内研究者と国内(学外)研究者との共同研究 (国外研究者を含まない))
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Natsumi Doi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Hiro Togari
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Kenji Minagi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Yuji Iwaoka
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 田井 章博([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.生体分子機能学分野])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Koichi Nakaoji
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Kazuhiko Hamada
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Masaaki Tatsuka
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) 2-O-Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage-induced abnormal spindle orientations

副題 任意
要約 任意

(英) The appropriate regulation of spindle orientation maintains proper tissue homeostasis and avoids aberrant tissue repair or regeneration. Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N-terminal-deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ/RhoGDI2/LyGDI) produced by caspase-3 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDIβ cleaved by caspase-3 activation acts as a determinant of radiation-induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDIβ expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDIβ expression in HeLa cells and identified a lipophilic derivative, 2-O-octadecylascorbic acid (2-OctadecylAA), as a novel RhoGDIβ inhibitor that ameliorated ionizing radiation-induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2-OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2-OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2-OctadecylAA are partly due to RhoGDIβ inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDIβ warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis.

キーワード 推奨
発行所 推奨
誌名 必須 Journal of Cellular Biochemistry([Wiley-Liss, Inc.])
(pISSN: 0730-2312, eISSN: 1097-4644)
ISSN 任意 1097-4644
ISSN: 0730-2312 (pISSN: 0730-2312, eISSN: 1097-4644)
Title: Journal of cellular biochemistry
Title(ISO): J Cell Biochem
Publisher: Wiley
 (NLM Catalog  (Wiley  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 122
必須 7
必須 739 751
都市 任意
年月日 必須 2021年 7月 初日
URL 任意
DOI 任意 10.1002/jcb.29908    (→Scopusで検索)
PMID 任意 33586155    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意 2-s2.0-85100830951
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.1002/jcb.29908

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) KeywordList.Keyword: RhoGDI

  4. (英) KeywordList.Keyword: ascorbic acid derivatives

  5. (英) KeywordList.Keyword: epithelial carcinoma

  6. (英) KeywordList.Keyword: ionizing radiation

  7. (英) KeywordList.Keyword: mitosis