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

Abstract:

:Previously, we showed that NO induces thymocyte apoptosis via a caspase-1-dependent mechanism [(1) ]. In the present study, we investigated the role of heme oxygenase, catalase, bax, and p53 in this process. The NO donor, S-nitroso-N-acetyl penicillamine (SNAP), induced DNA fragmentation in thymocytes in a time- and concentration-dependent way. SNAP (100 microM) induced 50--60% apoptosis; higher doses did not increase the rate of apoptosis significantly. SNAP decreased catalase and heme iron (Fe) levels without affecting superoxide dismutase, glutathione, or total Fe stores in thymocytes. SNAP significantly increased the expression of heme oxygenase 1 (HSP-32), p53, and bax but not bcl-2. Treatment with the heme oxygenase inhibitor, tin protoporphyrin IX inhibited SNAP-induced thymocyte apoptosis. Furthermore, thymocytes from p53 null mice were resistant to NO-induced apoptosis. Our data suggest that NO may induce its cytotoxic effects on thymocytes by modulating heme oxygenase and catalase activity as well as up-regulating pro-apoptotic proteins p53 and bax.

journal_name

J Leukoc Biol

authors

Gordon SA,Abou-Jaoude W,Hoffman RA,McCarthy SA,Kim YM,Zhou X,Zhang XR,Simmons RL,Chen Y,Schall L,Ford HR

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

87-95

issue

1

eissn

0741-5400

issn

1938-3673

journal_volume

70

pub_type

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