Fig. 9. A Mcl-1 inhibitor attenuated ischemic kidney injury.
WT mice were pretreated with the Mcl-1 inhibitor, S63845 and sacrificed 16 h after the ischemic insult. A–D S63845 treatment led to decreases in numbers of kidney neutrophils but increases in neutrophil apoptosis evaluated with flow cytometry analysis of cleaved caspase 3 (n = 4) (A) and cleaved caspase-9 and S100A9 co-staining (4 and 5) (B), in association with less injury, indicated by lower BUN (n = 6 and 7) (C) and a lower tubular injury score (n = 7 and 8) (D). E Mcl-1 inhibition with S63845 led to increased ex vivo bone marrow neutrophil apoptosis determined by cleaved caspase-3 flow cytometric analysis (n = 4). Of note, cleaved caspase-3 neutrophil counts vs. total neutrophil counts are presented in parenthesis. Scale bar: 50 μm for (B) and 100 μm for (D). Data are means ± SEM, *P < 0.05, **P < 0.01, analyzed using 2 tailed Student’s t test for (A–D); 2-way ANOVA followed by Tukey’s post hoc test for (E).
