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

Sherilyn A. Gordon, Walid Abou-Jaoude, Rosemary A. Hoffman, Susan A. McCarthy, Young Myeong Kim, Xin Zhou, Xiao Ru Zhang, Richard L. Simmons, Yue Chen, Laura Schall, Henri R. Ford

Research output: Contribution to journalArticle

33 Scopus citations

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 μM) 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.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalJournal of Leukocyte Biology
Volume70
Issue number1
StatePublished - 2001

Keywords

  • Bax
  • Catalase
  • Heme oxygenase
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Gordon, S. A., Abou-Jaoude, W., Hoffman, R. A., McCarthy, S. A., Kim, Y. M., Zhou, X., Zhang, X. R., Simmons, R. L., Chen, Y., Schall, L., & Ford, H. R. (2001). Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism. Journal of Leukocyte Biology, 70(1), 87-95.