Fig. 4.

Protective effects of NAC against DSS-induced colitis. NAC (100 mg/kg) was injected into mice for 3 consecutive days before DSS administration and treatment was continued during DSS administration for 7 consecutive days. (A) DAI scores were evaluated for 7 consecutive days. (B) Colon lengths of IDH2^-/- and IDH2^+/+ mice. (C) Hematoxylin and eosin-stained sections of colon tissues. (D) The average histological score for each element. (E) TUNEL staining of colon tissues. (F) Immunohistochemical staining of PUMA in colon tissues. (G) Immunofluorescent staining of acetyl-p65, (H) acetyl-H3, and (I) acetyl-H4 in colon tissues. Histograms represent the quantification of fluorescence intensity. The figure shows representative data of 3–6 independent experiments. Results are shown as the mean ± SD (n = 3–6 mice of each group). *P<0.05, versus DSS-treated wild-type mice. (J) Schematic diagram summarizing that IDH2 deficiency promotes an increase in the level of ROS, which suppresses the activity of HDAC. The low activity of HDAC enhances acetylation level of p65, a NF-κB subunit, which in turn, induces PUMA-mediated apoptosis. This axis was inhibited by the scavenging of ROS by NAC.