Figure 3
From: Dichotomy between RIP1- and RIP3-Mediated Necroptosis in Tumor Necrosis Factor-α-Induced Shock
Blocking necroptosis accelerates death and worsens organ damage after TNFα/zVAD-mediated hyperacute shock. (A) Mice were left untreated (open circles), injected intravenously with mouse TNFα alone (black squares) or in addition with zVAD (open triangles), zVAD + Nec-1 (open squares) or zVAD + TAT-crmA (black circles). Survival is presented as a Kaplan-Meyer plot. Whereas TNFα-treated mice die significantly later than TNFα/zVAD-treated animals (P < 0.01), both TNFα/zVAD/Nec-1- and TNFα/zVAD/TAT-crmA-treated mice died significantly earlier compared with TNFα/zVAD-treated mice (P < 0.02, n = 7). (B) Three h after TNFα-injection (basic experimental setting is identical to 3A), mice were euthanized, and kidneys were harvested and prepared for PAS-staining. Representative sections are shown, and a renal damage score was used for quantification. (C) Compared to the TNFα-treated group, significantly elevated renal damage was detected in the TNFα/zVAD-, TNFα/zVAD/Nec-1- and the TNFαzVAD/TAT-crmA-treated animals (n = 3). Scale bar, 20 µm.