FIGURE 8.

Effect of knocking down JNK1 and/or -2 on JNK translocation to mitochondria, mitochondria bioenergetics, and liver injury. A, effect of JNK1 and -2 ASO on JNK translocation to mitochondria induced by APAP treatment. B, effect of silencing JNK1 and -2 on mitochondria bioenergetics following APAP treatment C, effect of silencing JNK1, JNK2, or JNK1 and -2 on APAP-induced liver injury. One set of C56BL/6 mice were treated with control or JNK1 or JNK2 antisense (ASO) every other day for 2 weeks (7 doses). The other set of C56BL/6 mice were treated with control (double ASO dose) or JNK1 plus JNK2 antisense (ASO) every other day for 2 weeks (7 doses). Mice were subsequently treated with APAP (300 mg/kg) dissolved in warm PBS. For mitochondria measurements, livers were taken 2 h following APAP treatment, and mitochondria were separated from cytoplasm by differential centrifugation. Western blot analysis was performed using antisera against JNK with cytochrome oxidase and actin serving as loading controls, and mitochondria bioenergetics was measured as described under “Experimental Procedures.” In other experiments, serum ALT levels were measured 24 h after APAP treatment. n = 4–8 mice. Results are mean ± S.D. *, p < 0.05 versus APAP treatment alone.