Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism

Previously, we showed that NO induces thymocyte apoptosis via acaspase‐1‐dependent mechanism [1]. In the present study,we investigated the role of heme oxygenase, catalase, bax, and p53 inthis process. The NO donor, S‐nitroso‐N‐acetyl penicillamine (SNAP),induced DNA fragmentation in thymocytes in a time‐ andconcentration‐dependent way. SNAP (100 μM) induced 50–60%apoptosis; higher doses did not increase the rate of apoptosissignificantly. SNAP decreased catalase and heme iron (Fe) levelswithout affecting superoxide dismutase, glutathione, or total Fe storesin thymocytes. SNAP significantly increased the expression of hemeoxygenase 1 (HSP‐32), p53, and bax but notbcl‐2. Treatment with the heme oxygenase inhibitor, tinprotoporphyrin IX inhibited SNAP‐induced thymocyte apoptosis.Furthermore, thymocytes from p53 null mice were resistantto NO‐induced apoptosis. Our data suggest that NO may induce itscytotoxic effects on thymocytes by modulating heme oxygenase andcatalase activity as well as up‐regulating pro‐apoptotic proteinsp53 and bax.