INT206949
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
The down-regulation of PXR and CAR, along with FXR (Guo et al. 2003), would make the liver more susceptible to bile acid toxicity, which, coupled with the biliary hyperplasia, may exacerbate the hepatotoxic effects of methapyrilene administration. | |||||||||||||||
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The down-regulation of PXR may contribute to the hepatotoxicity of methapyrilene, as the ligand-induced activation of PXR serves to protect against bile acid toxicity resulting from several hepatotoxicants (Staudinger et al. 2001), whereas the resistance to bile acid toxicity is lost in mice lacking PXR (Xie et al. 2000). | |||||||||||||||
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If this is the case in vivo, we believe that adenovirus infection did not significantly affect PXR levels because both PKA and PKC are upregulated during adenovirus infection [33,34], keeping the expression of this protein in check except at the 24 hour time point when the balance between the expression of each enzyme might be disrupted since they are each uniquely involved at different stages of virus internalization and trafficking to the nucleus which occur during this timeframe [34]. | |||||||||||||||
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Although no appreciable changes in PXR and RXR mRNA levels were detected after administration of any of the vectors studied, post-translational modifications of these proteins and CYP itself such as phosphorylation, ubiquitination and redistribution between the nucleus and cytoplasm in response to virus-induced cell signaling cascades could account for the observed reduction in CYP during adenovirus infection and would not be readily detectable by the techniques used to assess changes in CYP, RXR and PXR described in this manuscript [30-32]. | |||||||||||||||
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Although no appreciable changes in PXR and RXR mRNA levels were detected after administration of any of the vectors studied, post-translational modifications of these proteins and CYP itself such as phosphorylation, ubiquitination and redistribution between the nucleus and cytoplasm in response to virus-induced cell signaling cascades could account for the observed reduction in CYP during adenovirus infection and would not be readily detectable by the techniques used to assess changes in CYP, RXR and PXR described in this manuscript [30-32]. | |||||||||||||||
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