Nitric Oxide Protects Thymocytes from γ-Irradiation-Induced Apoptosis in Correlation with Inhibition of p53 Upregulation and Mitochondrial Damage☆

Abstract Apoptosis plays a crucial role in clonal deletion in the thymus, and NO has been shown to prevent apoptosis in some cell types. Therefore, we examined the effect of NO on γ-irradiation-induced thymocyte apoptosis. Treatment of 5 Gy γ-irradiated thymocytes with 1 mM SNAP reduced cell death from 78 to 49% after 8 h incubation (spontaneous cell death in medium control cells was 26%). Coincubation with ZVAD blocked both the spontaneous cell death and the cell death induced by SNAP or γ-irradiation. The γ-irradiation-induced increase in caspase 3 and 6 activities was inhibited in the presence of SNAP. The increase in cytosolic cytochrome c as well as the decrease in mitochondrial membrane potential after γ-irradiation was inhibited in the presence of SNAP. SNAP treatment also decreased the p53 upregulation in γ-irradiated cells. In summary, we found that NO exerts a protective effect on mouse thymocyte apoptosis induced by γ-irradiation. The mechanism of this protective effect may involve inhibition of p53 upregulation and reduction in mitochondrial damage, with subsequent inhibition of downstream caspase activation.