Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.

摘要: The rise in type 1 diabetes (T1D) incidence recent decades is probably related to modifications environmental factors. Viruses are among the putative triggers of T1D. mechanisms regulating beta cell responses viruses, however, remain be defined. We have presently clarified signaling pathways leading apoptosis following exposure viral mimetic double-stranded RNA (dsRNA) and a diabetogenic enterovirus (Coxsackievirus B5). Internal dsRNA induces death via intrinsic mitochondrial pathway. In this process, activation dsRNA-dependent protein kinase (PKR) promotes eIF2α phosphorylation synthesis inhibition, downregulation antiapoptotic Bcl-2 myeloid leukemia sequence (Mcl-1). Mcl-1 decrease results release BH3-only Bim, which activates pathway apoptosis. Indeed, Bim knockdown prevented both dsRNA- Coxsackievirus B5-induced death, counteracted proapoptotic effects silencing. These observations indicate that balance between key factor survival during infections.