Dimethylsphingosine Regulates Intracellular pH and Ca^<2+> in Human Monocytes

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著者

    • Lee Eun-Hee LEE Eun-Hee
    • Laboratory of Pharmacology, College of Pharmacy and Research Institute for Drug Development, Pusan National University
    • Lee Yun-Kyung LEE Yun-Kyung
    • Laboratory of Pharmacology, College of Pharmacy and Research Institute for Drug Development, Pusan National University
    • KIM Jae-Ho
    • Department of Physiology, College of Medicine, Pusan National University
    • OKAJIMA Fumikazu
    • Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University
    • IM Dong-Soon
    • Laboratory of Pharmacology, College of Pharmacy and Research Institute for Drug Development, Pusan National University

抄録

Dimethylsphingosine (DMS) was first reported as an inhibitor of protein kinase C and later has been used as a specific inhibitor of sphingosine kinase. Furthermore, its anti-cancer effect has become a basis for development of chemotherapy. Nevertheless, its anti-neoplastic mechanism has poorly been understood. In the present study, we observed that DMS increased intracellular pH and Ca<sup>2+</sup> concentration in U937 human monocytes. To further characterize these DMS-induced actions, we employed structurally-related sphingolipids and specific pharmacological tools such as inhibitors of protein kinase C and Na<sup>+</sup>/H<sup>+</sup> exchanger and found that the two responses of DMS were mimicked by four stereoisomers of sphingosine and two isomers to dihydrosphingosine, but not with sphingosine 1-phosphate, sphingosyl-phosphorylcholine, and C2-ceramide. Furthermore, DMS-induced pH increase was independent of Na<sup>+</sup>/H<sup>+</sup> exchanger activity. We also characterized the interrelationship between DMS-induced pH increase and DMS-induced Ca<sup>2+</sup> increase. Since DMS is considered to be a good anti-cancer candidate, our characterization of DMS actions provides useful information for development of DMS chemotherapy.<br>

収録刊行物

  • Journal of pharmacological sciences

    Journal of pharmacological sciences 100(4), 289-296, 2006-04-20

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018239959
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    7884953
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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