Exposure to the Viral By-Product dsRNA or Coxsackievirus B5 Triggers Pancreatic Beta Cell Apoptosis via a Bim / Mcl-1 Imbalance
Figure 1
Internal dsRNA induces beta cell death via the mitochondrial pathway of apoptosis.
A. INS-1E cells were transfected with the synthetic dsRNA polyinosinic-polycytidylic acid (PIC) and apoptosis was evaluated at different time points using nuclear dyes as described in Methods (n = 5, *P<0.01 vs. untreated). B. BAX localization was studied by immunocytochemistry in INS-1E cells exposed or not to internal dsRNA for 24h. Pictures are representative of 4 independent experiments; arrows indicate BAX mitochondrial localization, similar to the ATP Synthase (mitochondrial marker) C. Cytochrome c release in INS-1E cells treated for 24h in the presence or absence of intracellular dsRNA. Pictures are representative of 4 independent experiments. D. Western blot quantified by densitometry of cytoplasmic protein fractions in INS-1E cells transfected or not with dsRNA for 24h (n = 4, *P<0.01 vs. untreated). E. Western blot analysis and densitometry of cleaved caspases 9 and 3 after INS-1E cells exposure to internal dsRNA at different time points (n = 5–6, *P<0.05, **P<0.01 vs. untreated). Data are mean ± SEM.