CoCl2 induces PC12 cells apoptosis through p53 stability and regulating UNC5B.

ABSTRACT

The receptor uncoordinated 5B (UNC5B) induces apoptosis in the absence of its cognate ligand netrin-1. However, the role of UNC5B in hypoxia-induced apoptosis is not known. Here, we have demonstrated the biological functions of UNC5B in hypoxia-induced apoptosis and related regulatory pathways and examined the effects of UNC5B on p53-dependent apoptosis in PC12 cells under hypoxic conditions. First, we characterized p53-dependent PC12 cell death induced by CoCl2. Our data showed that CoCl2 increased p53 stabilization and transcriptional activity. The downregulation of p53 expression with specific small interfering RNA (p53 siRNA) in CoCl2-treated PC12 cells caused reduction in apoptosis, UNC5B expression, and p21 expression. Moreover, in PC12 cells, ectopic expression of UNC5B significantly enhanced apoptosis, while silencing of UNC5B with siRNA significantly inhibited apoptosis. In addition, netrin-1 significantly inhibited CoCl2-induced p53 stability and UNC5B expression and CoCl2-induced caspase-3 activity and cell death. Collectively, these results demonstrate a novel role for p53 in the control of CoCl2-induced apoptosis through the regulation of UNC5B.