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.
Current Cancer Drug Targets
Title: Bid Mediates Anti-Apoptotic COX-2 Induction Through the IKKβ/NFκB Pathway Due to 5-MCDE Exposure
Volume: 10 Issue: 1
Author(s): W. Luo, J. Li, D. Zhang, T. Cai, L. Song, X.-M. Yin, D. Desai, S. Amin, J. Chen and C. Huang
Affiliation:
Keywords: Bid, COX-2, 5-MCDE, NFκB, apoptosis
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.
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Cite this article as:
Luo W., Li J., Zhang D., Cai T., Song L., Yin X.-M., Desai D., Amin S., Chen J. and Huang C., Bid Mediates Anti-Apoptotic COX-2 Induction Through the IKKβ/NFκB Pathway Due to 5-MCDE Exposure, Current Cancer Drug Targets 2010; 10 (1) . https://dx.doi.org/10.2174/156800910790980160
DOI https://dx.doi.org/10.2174/156800910790980160 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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