Figure 5. Regulation of JNK and Chop by ROS in p38α^Δhep and Ikkβ^Δhep mice.

(A, B) Mice of the indicated genotypes were fed either BHA-containing (0.7%) or regular chow for 2 days, and then injected with DEN. JNK activity was determined by immunecomplex kinase assays of liver lysates prepared at the indicated times after DEN injection (A). MKK4 phosphorylation was analyzed by immunoblotting (B). (C) Mice were injected with DEN and their livers isolated at the indicated times, homogenized and Chop expression was examined by immunoblotting. (D) Mice of the indicated genotypes were injected with DEN, total liver RNA was extracted 4 or 10 hrs later, and expression of Chop mRNA was quantified. Results are means ± SEM (n=4). *, p<0.05 vs. control mice (F/F). (E) p38α^Δhep mice were fed either BHA-supplemented (0.7%) or regular chow (Cont.) for 2 days, and then injected with DEN. Total liver RNA was extracted 4 and 12 hrs later and expression of the indicated genes was measured as above. Results are means ± SEM (n=4). *, p<0.05. (F) p38α^Δhep mice were infected with adenovirus expressing Hsp25 or a control adenovirus 20 hrs before DEN injection. Liver lysates prepared at the indicated times after DEN injection, were analyzed for Chop expression. (G) p38α^F/F mice were infected with adenovirus expressing IRF1 or a control adenovirus 20 hrs before DEN injection. Liver lysates prepared 8 hrs after DEN injection were analyzed for IRF1 and Chop expression.