Fig. 7.

SIRT2 deficiency prevents acetaminophen (APAP)-induced liver cell death. a Representative H&E staining images of wild-type (WT) and SIRT2-deficient (SIRT2-KO) mice liver sections showing degenerative changes (arrows) when injected with 100 mg/kg APAP intraperitoneally. SIRT2-KO mice show reduced degenerative changes. n = 5 mice per group/time point. Scale bar = 20 µM. b Representative TUNEL staining images of WT and SIRT2-KO mice liver sections showing TUNEL-positive cells (brown nuclei) 24 h post injection with 100 mg/kg APAP intraperitoneally. n = 5 mice per group. c Graph showing the percentage of TUNEL-positive cells in WT and SIRT2-KO mice liver sections. Mice were sacrificed 24 h post 100 mg/kg APAP intraperitoneal injection. n = 5 mice per group. Scale bar = 20 µM Data are presented as mean ± s.d. *p < 0.05. Student’s t-test was used to calculate the p-values. d Graph depicting the levels of serum alanine aminotransferase (ALT) in WT and SIRT2-KO mice. Mice were sacrificed at different time points after 100 mg/kg acetaminophen (APAP) intraperitoneal injection. n = 5 mice per group. Data are presented as mean ± s.d. *p < 0.05. Two-way ANOVA was used to calculate the p-values. e Graph depicting the levels of serum aspartate aminotransferase (AST) in WT and SIRT2-KO mice. Mice were sacrificed at different time points after 100 mg/kg APAP intraperitoneal injection. n = 5 mice per group. Data are presented as mean ± s.d. *p < 0.05. Two-way ANOVA was used to calculate the p-values. f Western blotting images depicting the acetylation of endogenous JNK in the liver lysates of WT and SIRT2-KO mice injected with vehicle or 100 mg/kg APAP. JNK was immunoprecipitated and assessed for the acetylation of JNK. Whole cell lysates (WCLs) were probed for the protein levels of SIRT2 by western blotting. g Western blotting images depicting the phosphorylation of endogenous JNK in the liver lysates of WT and SIRT2-KO mice injected with vehicle or 100 mg/kg APAP. WCLs were probed for phosphorylation of JNK and total protein levels of SIRT2 by western blotting. h Graph showing the survival of WT and SIRT2-KO mice injected with high dose of APAP (600 mg/kg; APAP). n = 20 mice per group