| dc.contributor.author | Delaporte, Enock. | en_US |
| dc.date.accessioned | 2014-10-21T12:38:12Z | |
| dc.date.available | 1995 | |
| dc.date.issued | 1995 | en_US |
| dc.identifier.other | AAINN16009 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55153 | |
| dc.description | Interferon (IFN) and interferon inducers depress the hepatic and extrahepatic expression of constitutive and inducible cytochrome P450s through a pretranslational mechanism which downregulates the mRNA encoding specific P450 apoproteins. The IFN effect is independent of the mechanism by which the P450 is induced but requires the de novo synthesis of an unknown intermediate protein. We investigated the possible pretranslational mechanisms by which IFN$\alpha/\beta$ (induced with polyIC, 10 mg/kg) depresses P450 expression by examining the degradation of induced CYP1A1 and CYP1A2 mRNAs after inhibiting de novo transcription with actinomycin D (1 mg/kg). Steady state mRNAs analyzed by Northern and slot blotting showed that polyIC significantly augmented the loss of CYP1A1 and CYP1A2 mRNA. We used a geneticaliy engineered cell line to show a role for the nucleus in CYP1A1 downregulation by recombinant IFN. We further characterized the pretranslational loss of P450s by performing nuclear run-on transcription assays with nuclei isolated from the liver of male rats. We examined the effect of IFN$\alpha/\beta$ on the rates of transcription of CYP1A1 and CYP1A2 genes. The results showed that polyIC decreased the rate of transcription of both CYP1A1 and CYP1A2 suggesting that IFN$\alpha/\beta$ production also depresses gene transcription. The results of these studies suggest that transcriptional as well as posttranscriptional events could account for the pretranslational mechanism by which IFN downregulates P450 expression. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1995. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.subject | Biology, Animal Physiology. | en_US |
| dc.title | Mechanisms of interferon mediated downregulation of cytochrome P450 enzymes. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
