Discovery of a novel compound: Insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death

Yuzo Nakagawa-Yagi, Dong Kug Choi, Nobuo Ogane, Shin Ichi Shimada, Motohide Seya, Takashi Momoi, Takashi Ito, Yoshiyuki Sakaki

研究成果: ジャーナルへの寄稿記事

21 引用 (Scopus)

抄録

The exposure of humans and experimental animals to certain industrial toxins such as acrylamide is known to cause nerve damage classified as axonopathy, but the mechanisms involved are poorly understood. Here we show that acrylamide induces morphological changes and tyrosine phosphorylation of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), a member of the FAK subfamily, in human differentiating neuroblastoma SH-SY5Y cells. Furthermore, we identified a novel molecule designated 'compound-1' that inhibits the morphological and biochemical events. Daily oral administrations of the compound also effectively alleviated behavioral deficits in animals elicited by acrylamide in inclined plane testing, landing foot spread testing and rota-rod performance testing. The compound also effectively inhibited the biological and biochemical responses caused by another axonopathy inducer, colchicine, including tyrosine phosphorylation of Pyk2, formation of an 85-kDa poly(ADP-ribose)polymerase (PARP) fragment and apoptosis-associated induction of the NAPOR gene as well as neuronal cell death. Our findings not only provide insight into FAK and Pyk2 functions in neuronal cells, but may also be important in the development of therapeutic agents for peripheral neuropathy and neurodegeneration

元の言語英語
ページ(範囲)8-19
ページ数12
ジャーナルBrain Research
909
発行部数1-2
DOI
出版物ステータス出版済み - 8 3 2001
外部発表Yes

Fingerprint

Focal Adhesion Kinase 2
Focal Adhesion Protein-Tyrosine Kinases
Acrylamide
Colchicine
Cell Death
Tyrosine
Phosphorylation
Poly(ADP-ribose) Polymerases
Peripheral Nervous System Diseases
Neuroblastoma
Oral Administration
Foot
Apoptosis
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

これを引用

Discovery of a novel compound : Insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death. / Nakagawa-Yagi, Yuzo; Choi, Dong Kug; Ogane, Nobuo; Shimada, Shin Ichi; Seya, Motohide; Momoi, Takashi; Ito, Takashi; Sakaki, Yoshiyuki.

:: Brain Research, 巻 909, 番号 1-2, 03.08.2001, p. 8-19.

研究成果: ジャーナルへの寄稿記事

Nakagawa-Yagi, Yuzo ; Choi, Dong Kug ; Ogane, Nobuo ; Shimada, Shin Ichi ; Seya, Motohide ; Momoi, Takashi ; Ito, Takashi ; Sakaki, Yoshiyuki. / Discovery of a novel compound : Insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death. :: Brain Research. 2001 ; 巻 909, 番号 1-2. pp. 8-19.
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