Faculty Collaboration Database

Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism. J Leukoc Biol 2001 Jul;70(1):87-95

Date

07/04/2001

Pubmed ID

11435490

Scopus ID

2-s2.0-0034964317 (requires institutional sign-in at Scopus site)   35 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 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.

Author List

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

Author

Laura Cassidy PhD Associate Dean, Institute Director, Professor in the Institute for Health and Humanity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Catalase
Coculture Techniques
Enzyme Induction
Erythrocytes
Gene Expression
Glutathione
Heme
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Iron
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Knockout
Nitric Oxide
Nitric Oxide Donors
Oxidative Stress
Penicillamine
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
S-Nitroso-N-Acetylpenicillamine
Superoxide Dismutase
Thymus Gland
Tumor Suppressor Protein p53
bcl-2-Associated X Protein