INT206949

Context Info Confidence 0.57 First Reported 2007 Last Reported 2008 Negated 2 Speculated 0 Reported most in Body Documents 3 Total Number 5 Disease Relevance 2.50 Pain Relevance 0.45

nucleus (Nr1i2)

Anatomy Link Frequency nucleus 3 bile 2 Nr1i2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Bile 10 98.12 Kinase C 3 96.20 Paracetamol 2 56.48 cytokine 3 5.00 ketamine 3 5.00 anesthesia 3 5.00 Inflammation 3 5.00 Inflammatory stimuli 3 5.00 Inflammatory mediators 3 5.00

Disease Link Frequency Relevance Heat Adenovirus Infection 21 99.54 Hepatotoxicity 59 99.08 Injury 4 97.48 Targeted Disruption 3 96.92 Toxicity 68 96.20 Repression 10 95.04 Biliary Cancer 4 94.84 Stress 52 72.24 Infection 30 56.48 Hepatitis 2 47.36

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.

Regulation (regulation) of PXR in bile associated with toxicity, bile and biliary cancer

1) Confidence 0.57 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852695 Disease Relevance 0.97 Pain Relevance 0.24

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).

Regulation (regulation) of PXR in bile associated with toxicity, bile and hepatotoxicity

2) Confidence 0.42 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852695 Disease Relevance 0.64 Pain Relevance 0.16

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].

Neg (not) Regulation (affect) of PXR in nucleus associated with adenovirus infection

3) Confidence 0.14 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.25 Pain Relevance 0.05

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].

Regulation (changes) of PXR in nucleus associated with adenovirus infection

4) Confidence 0.06 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.25 Pain Relevance 0

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].

Neg (no) Regulation (changes) of PXR in nucleus associated with adenovirus infection

5) Confidence 0.06 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.38 Pain Relevance 0

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