論文

査読有り
2012年6月

Cordycepin as a sensitizer to tumour necrosis factor (TNF)-α-induced apoptosis through eukaryotic translation initiation factor 2α (eIF2α)- and mammalian target of rapamycin complex 1 (mTORC1)-mediated inhibition of nuclear factor (NF)-κB

Clinical and Experimental Immunology
  • M. Kadomatsu
  • ,
  • S. Nakajima
  • ,
  • H. Kato
  • ,
  • L. Gu
  • ,
  • Y. Chi
  • ,
  • J. Yao
  • ,
  • M. Kitamura

168
3
開始ページ
325
終了ページ
332
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/j.1365-2249.2012.04580.x

Cordycepin (3′-deoxyadenosine) is one of the major bioactive substances produced by Cordyceps militaris, a traditional medicinal mushroom. Cordycepin possesses several biological activities, including both pro-apoptotic and anti-apoptotic properties. In the present report, we investigated an effect of cordycepin on the survival of cells exposed to tumour necrosis factor (TNF)-α. We found that subtoxic doses of cordycepin increased susceptibility of cells to TNF-α-induced apoptosis. It was associated with suppression of nuclear factor-κB (NF-κB), a major prosurvival component involved in TNF-α signalling. The adenosine transporter and A 3 adenosine receptor, but not A 1 and A 2 adenosine receptors, mediated both anti-NF-κB and pro-apoptotic effects. We found that cordycepin had the potential to phosphorylate eukaryotic translation initiation factor 2α (eIF2α) and that activation of eIF2α mimicked the suppressive effect of cordycepin on the NF-κB pathway. Furthermore, activation of eIF2α sensitized cells to TNF-α-induced apoptosis. To identify molecular events downstream of eIF2α, the role of mammalian target of rapamycin complex 1 (mTORC1) was examined. Selective activation of 3eIF2α, as well as treatment with cordycepin, caused phosphorylation of mTORC1. Rapamycin, an inhibitor of mTORC1, significantly reversed the suppressive effects of eIF2α on NF-κB. These results suggest that cordycepin sensitizes cells to TNF-α-induced apoptosis, at least in part, via induction of the eIF2α-mTORC1 pathway and consequent suppression of NF-κB. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.

リンク情報
DOI
https://doi.org/10.1111/j.1365-2249.2012.04580.x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22519596
ID情報
  • DOI : 10.1111/j.1365-2249.2012.04580.x
  • ISSN : 0009-9104
  • ISSN : 1365-2249
  • PubMed ID : 22519596
  • SCOPUS ID : 84859949262

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