Bid mediates anti-apoptotic COX-2 induction through the IKKβ/NFκB pathway due to 5-MCDE exposure

W. Luo, J. Li, D. Zhang, T. Cai, L. Song, Xiao-Ming Yin, D. Desai, S. Amin, J. Chen, C. Huang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Although Bid is considered to be a cell apoptotic mediator, current studies suggest that it has a possible role in cell survival for mouse embryonic fibroblasts (MEFs) in response to low doses of anti-(±)-5- methylchrysene-1,2-diol-3,4-epoxide (≤0.25μM) (5-MCDE). We found that the exposure of MEFs to 0.25 μM 5-MCDE resulted in a slight apoptotic induction, while this apoptotic response was substantially increased in the Bid knockout MEFs (Bid-/-), suggesting that there is a Bid-mediated anti-apoptotic function in this response. This notion was further supported by the findings that re-constitution expression of Bid into Bid-/- cells could inhibit the increased apoptosis. Further studies show that the antiapoptotic function of Bid was associated with its mediation of COX-2 expression. This conclusion was based the reduction of COX-2 expression in Bid-/- cells, the restoration of low sensitivity to 5-MCDE-induced apoptosis by the introduction of Bid into Bid-/- cells, and increased sensitivity of WT MEFs to 5-MCDE-induced apoptosis by the knockdown of COX-2 expression. Furthermore, we found that Bid mediated COX-2 expression through the IKKβ/NFκB pathway because the deficiency of Bid in Bid-/- MEFs resulted in the blockade of IKK/NFκB activation and knockout of IKKβ caused abrogation of COX-2 expression induced by 5-MCDE. Collectively, our results demonstrate that Bid is critical for COX-2 induction through the IKKβ/NFκB pathway, which mediates its anti-apoptotic function, in cell response to low doses of 5-MCDE exposure.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalCurrent Cancer Drug Targets
Volume10
Issue number1
DOIs
StatePublished - Feb 2010
Externally publishedYes

Fingerprint

Fibroblasts
Apoptosis
Constitution and Bylaws
Knockout Mice
Cell Survival

Keywords

  • 5-MCDE
  • Apoptosis
  • Bid
  • COX-2
  • NFκB

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Cancer Research

Cite this

Bid mediates anti-apoptotic COX-2 induction through the IKKβ/NFκB pathway due to 5-MCDE exposure. / Luo, W.; Li, J.; Zhang, D.; Cai, T.; Song, L.; Yin, Xiao-Ming; Desai, D.; Amin, S.; Chen, J.; Huang, C.

In: Current Cancer Drug Targets, Vol. 10, No. 1, 02.2010, p. 96-106.

Research output: Contribution to journalArticle

Luo, W, Li, J, Zhang, D, Cai, T, Song, L, Yin, X-M, Desai, D, Amin, S, Chen, J & Huang, C 2010, 'Bid mediates anti-apoptotic COX-2 induction through the IKKβ/NFκB pathway due to 5-MCDE exposure', Current Cancer Drug Targets, vol. 10, no. 1, pp. 96-106. https://doi.org/10.2174/156800910790980160
Luo, W. ; Li, J. ; Zhang, D. ; Cai, T. ; Song, L. ; Yin, Xiao-Ming ; Desai, D. ; Amin, S. ; Chen, J. ; Huang, C. / Bid mediates anti-apoptotic COX-2 induction through the IKKβ/NFκB pathway due to 5-MCDE exposure. In: Current Cancer Drug Targets. 2010 ; Vol. 10, No. 1. pp. 96-106.
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AU - Li, J.

AU - Zhang, D.

AU - Cai, T.

AU - Song, L.

AU - Yin, Xiao-Ming

AU - Desai, D.

AU - Amin, S.

AU - Chen, J.

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AB - Although Bid is considered to be a cell apoptotic mediator, current studies suggest that it has a possible role in cell survival for mouse embryonic fibroblasts (MEFs) in response to low doses of anti-(±)-5- methylchrysene-1,2-diol-3,4-epoxide (≤0.25μM) (5-MCDE). We found that the exposure of MEFs to 0.25 μM 5-MCDE resulted in a slight apoptotic induction, while this apoptotic response was substantially increased in the Bid knockout MEFs (Bid-/-), suggesting that there is a Bid-mediated anti-apoptotic function in this response. This notion was further supported by the findings that re-constitution expression of Bid into Bid-/- cells could inhibit the increased apoptosis. Further studies show that the antiapoptotic function of Bid was associated with its mediation of COX-2 expression. This conclusion was based the reduction of COX-2 expression in Bid-/- cells, the restoration of low sensitivity to 5-MCDE-induced apoptosis by the introduction of Bid into Bid-/- cells, and increased sensitivity of WT MEFs to 5-MCDE-induced apoptosis by the knockdown of COX-2 expression. Furthermore, we found that Bid mediated COX-2 expression through the IKKβ/NFκB pathway because the deficiency of Bid in Bid-/- MEFs resulted in the blockade of IKK/NFκB activation and knockout of IKKβ caused abrogation of COX-2 expression induced by 5-MCDE. Collectively, our results demonstrate that Bid is critical for COX-2 induction through the IKKβ/NFκB pathway, which mediates its anti-apoptotic function, in cell response to low doses of 5-MCDE exposure.

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