Figure 1.

Comparison of knockdown of MKK4 versus MKK7 in acetaminophen induced necrotic liver injury model. After injection of control or MKK4 ASO or MKK7 ASO, the mice were treated with APAP (300 mg/kg) intraperitoneally. (a) Western blots of MKK4 and MKK7 knockdown in liver lysate. Hela cell lysate used as positive control. (b) Quantitative PCR of MKK4 or MKK7 in liver of control ASO versus MKK4 or MKK7 ASO-injected mice. MKK4 or MKK7 mRNA was normalized by housekeeping gene TBP (TATA box binding protein); *P<0.05; n=5 mice per each group. (c) Serum ALT 24 h after APAP. Mean±S.D., n=5 per group; *P<0.05 (t-test), Control versus MKK4 or MKK7 KD. (d) Representative hematoxylin and eosin-stained liver histology 24 h after APAP. Scale bars represent 100 μm. (e) Effect of control, MKK4 ASO or MKK7 ASO on covalent binding of NAPQI. Western blot of liver homogenate was prepared 1 h after APAP (300 mg/kg) using anti-adduct antisera. (* indicates versus control PBS). (f) Liver GSH levels. Mean±S.D., n=5 per group and time point