Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis
J. Clin. Invest. Ali Canbay, et al. 112:152 doi:10.1172/JCI17740 [Go to this article.]

Figure 2
Liver injury and cytochrome c release are reduced in Ctsb^–/– and R-3032–treated Ctsb^+/+ mice. Ctsb^+/+ and Ctsb^–/– mice were BDL for 3 days as described in Methods. (a) Fixed liver specimens were analyzed by TUNEL assay to identify apoptotic hepatocytes (arrows). (b) The number of TUNEL-positive cells was significantly higher in Ctsb^+/+ BDL mice than in sham-operated control or Ctsb^–/– and R-3032–treated Ctsb^+/+ BDL mice (P < 0.0001, n = 4 for each experimental group). (c) Cytosolic and mitochondrial fractions were prepared as described in Methods. Aliquots of 50 μg of cytosolic protein were subjected to SDS-PAGE and immunoblotted for cytochrome c. Release of cytochrome c in the cytosol was higher in Ctsb^+/+ BDL livers compared with Ctsb^–/– and R-3032–treated Ctsb^+/+ BDL mice. A representative immunoblot from one animal from each group is shown, together with densitometric analysis of multiple immunoblots (n = 3 animals for each group). (d) Serum ALT values are significantly greater in Ctsb^+/+ than in Ctsb^–/– (P < 0.005, n = 4 for each experimental group) and R-3032–treated Ctsb^+/+ mice 3 days after BDL (P < 0.0001, n = 4 for each experimental group). U/l, units per liter.