Figure 5 | Scientific Reports

Figure 5

From: ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways

Figure 5

ER stress induction is a prerequisite for the JNK-mediated apoptotosis and necroptosis in PC12 cells.

(A) Temporal expression profiles of ER stress markers, JNK signaling intermediates, caspase-3 and RIPK1 (a marker for necroptosis) in Hrs-silenced PC12 cells. For electromobility shift-based detection of phosphorylated RIPK1, samples were separated by 10% Phos-tag® gels. The black arrowhead and arrow indicate total and phosphorylated RIPK1, respectively. (B) Co-immunoprecipitation revealed a physical interaction between RIPK1 and RIPK3 in Hrs-silenced PC12 cells. (C) The expression of phosphorylated JNK1/2/3 in Hrs-depleted cells was markedly suppressed by the ER stress inhibitors (4-PBA and tangeretin) or the RIPK1-specific inhibitor (necrostatin-1). (D) JNK1/2/3 phosphorylation in Hrs-depleted PC12 cells was reduced by the genetic ablation of RIPK1.

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