| First Author | Tharappel JC | Year | 2003 |
| Journal | Toxicol Sci | Volume | 75 |
| Issue | 2 | Pages | 300-8 |
| PubMed ID | 12883078 | Mgi Jnum | J:126216 |
| Mgi Id | MGI:3760719 | Doi | 10.1093/toxsci/kfg201 |
| Citation | Tharappel JC, et al. (2003) Cell proliferation and apoptosis are altered in mice deficient in the NF-kappaB p50 subunit after treatment with the peroxisome proliferator ciprofibrate. Toxicol Sci 75(2):300-8 |
| abstractText | We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-kappaB DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-kappaB p50 gene (p50-/-). Wild-type and p50-/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-kappaB DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50-/- mice. The untreated p50-/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild-type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild-type mice than in ciprofibrate-fed p50-/- mice. The apoptotic index was low in wild-type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50-/- mice compared to wild-type mice; apoptosis was reduced in p50-/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50-/- mice than in untreated control mice; c-Jun mRNA levels increased, whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. The c-Jun and JunB protein levels were the same in untreated wild-type and p50-/- mice and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50-/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-kappaB contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate. |
