Induction of adaptive response and enhancement of PC12 cell tolerance by lipopolysaccharide primarily through the upregulation of glutathione S-transferase A3 via Nrf2 activation

Yo Omata, Yoshiro Saito, Katsuhide Fujita, Yoko Ogawa, Keiko Nishio, Yasukazu Yoshida, Etsuo Niki

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Increasing evidence indicates that reactive oxygen species and other physiologically existing oxidative stimuli upregulate the antioxidant system, thereby triggering the adaptive response. In this study, we focused on adaptive cytoprotection induced by lipopolysaccharide (LPS), which induces oxidative stress and inflammatory cytokines, in PC12 cells, a model of the neuronal cell. After treating PC12 cells with LPS at sublethal concentrations, we found that they developed resistance to subsequent oxidative stress induced by 13S-hydroperoxy-9Z,11E-octadecadienoic acid and 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium. To determine the underlying molecular mechanisms responsible for an adaptive response induced by LPS, we studied the changes in the antioxidant system. LPS treatment resulted in an increase in the gene expression of glutathione S-transferase A3 (GST-A3) by up to 60-fold as well as in GST enzyme activity. A GST inhibitor and GST A3 small interfering RNA effectively attenuated the adaptive response. The nuclear factor erythroid 2 p45-related factor 2 (Nrf2) was transcriptionally activated by LPS. Nrf2 small interfering RNA effectively attenuated the increase in GST A3 mRNA level as well as the adaptive response induced by LPS. In addition, peripheral injection of LPS at sublethal concentrations increased GST enzyme activity in mouse brain. These findings, taken together, indicate that stimulation with LPS at sublethal concentrations induces an adaptive response and enhances PC12 cell tolerance, primarily through the induction of GST A3 via the transcriptional activation of the Nrf2 signaling pathway. Crown

本文言語English
ページ(範囲)1437-1445
ページ数9
ジャーナルFree Radical Biology and Medicine
45
10
DOI
出版ステータスPublished - 2008 11 15
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

フィンガープリント 「Induction of adaptive response and enhancement of PC12 cell tolerance by lipopolysaccharide primarily through the upregulation of glutathione S-transferase A3 via Nrf2 activation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル