Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

• Goshima Yoshio

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Usui Hiroshi

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Shiozawa Takahito

  Graduate School of Environment and Information Sciences, Yokohama National University, Japan

• Hida Tomonobu

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Kuraoka Satoshi

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Takeshita Sayumi

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Yamashita Naoya

  Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan

• Ichikawa Yasushi

  Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Japan

• Kamiya Yoshinori

  Department of Anesthesiology, Yokohama City University Graduate School of Medicine, Japan

• Gotoh Takahisa

  Department of Anesthesiology, Yokohama City University Graduate School of Medicine, Japan

• Gotoh Toshiyuki

  Graduate School of Environment and Information Sciences, Yokohama National University, Japan

抄録

Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI–labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 114 (2), 168-179, 2010

  公益社団法人 日本薬理学会

キーワード

• axonal transport
• automated system
• chloromethylbenzamido dialkylcarbocyanine (CM-DiI)
• anti-cancer drug
• dorsal root ganglia

詳細情報

• CRID: 1390282680156659456
• NII論文ID: 10027746571
• NII論文ID: 130000336362
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.09352fp
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 10857415
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10857415
• Web Site: https://search.jamas.or.jp/link/ui/2011175826
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可