論文

査読有り
2009年9月

Oxidative Stress Induces Anti-Hepatitis C Virus Status via the Activation of Extracellular Signal-Regulated Kinase

HEPATOLOGY
  • Masahiko Yano
  • Masanori Ikeda
  • Ken-ichi Abe
  • Yoshinari Kawai
  • Misao Kuroki
  • Kyoko Mori
  • Hiromichi Dansako
  • Yasuo Ariumi
  • Shougo Ohkoshi
  • Yutaka Aoyagi
  • Nobuyuki Kato
  • 全て表示

50
3
開始ページ
678
終了ページ
688
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/hep.23026
出版者・発行元
JOHN WILEY & SONS INC

Recently, we reported that beta-carotene, vitamin D(2), and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma. cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti-HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved m their anti-HCV activities. However, the molecular mechanism by which oxidative stress induces anti-HCV status remains unknown. Oxidative stress is also known to activate extracellular signal-regulated kinase (ERK). Therefore, we hypothesized that oxidative stress induces anti-HCV status via the mitogen activated protein kinase (MAPK)/ERK kinase (MEK)-ERK1/2 signaling pathway. In this study, we found that the MEK1/2-spedfic inhibitor U0126 abolished the anti-HCV activities of the three nutrients in a dose-dependent manner. Moreover, U0126 significantly attenuated the anti-HCV activities of polyunsaturated fatty acids, interferon-gamma, and cyclosporine A, but not statins. We further demonstrated that, with the exception of the statins, all of these anti-HCV nutrients and reagents actually induced activation of the MEK-ERK1/2 signaling pathway, which was inhibited or reduced by treatment not only with U0126 but also with vitamin E We also demonstrated that phosphorylation of ERK1/2 by cyclosporine A was attenuated with N-acetylcysteine treatment and led to the negation of inhibition of HCV RNA replication. We propose that a cellular process that follows ERK1/2 phosphorylation and is specific to oxidative stimulation might lead to down-regulation of HCV RNA replication. Conclusion: Our results demonstrate the involvement of the MEK-ERK1/2 signaling pathway in the anti-HCV status induced by oxidative stress in a broad range of anti-HCV reagents. This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication. (HEPATOLOGY 2009;50: 678-688.)

リンク情報
DOI
https://doi.org/10.1002/hep.23026
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19492433
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000269551100006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/hep.23026
  • ISSN : 0270-9139
  • eISSN : 1527-3350
  • PubMed ID : 19492433
  • Web of Science ID : WOS:000269551100006

エクスポート
BibTeX RIS