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Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53‐dependent mechanism
Author(s) -
Gordon Sherilyn A.,
AbouJaoude Walid,
Hoffman Rosemary A.,
McCarthy Susan A.,
Kim YoungMyeong,
Zhou Xin,
Zhang XiaoRu,
Simmons Richard L.,
Chen Yue,
Schall Laura,
Ford Henri R.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.1.87
Subject(s) - heme oxygenase , apoptosis , catalase , superoxide dismutase , biology , heme , snap , thymocyte , nitric oxide , microbiology and biotechnology , biochemistry , oxidative stress , immunology , endocrinology , enzyme , cd8 , immune system , computer graphics (images) , computer science
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 not bcl‐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 proteins p53 and bax.