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...

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Veröffentlicht in:Journal of leukocyte biology 2001-07, Vol.70 (1), p.87-95
Hauptverfasser: Gordon, Sherilyn A., Abou‐Jaoude, Walid, Hoffman, Rosemary A., McCarthy, Susan A., Kim, Young‐Myeong, Zhou, Xin, Zhang, Xiao‐Ru, Simmons, Richard L., Chen, Yue, Schall, Laura, Ford, Henri R.
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container_issue 1
container_start_page 87
container_title Journal of leukocyte biology
container_volume 70
creator Gordon, Sherilyn A.
Abou‐Jaoude, Walid
Hoffman, Rosemary A.
McCarthy, Susan A.
Kim, Young‐Myeong
Zhou, Xin
Zhang, Xiao‐Ru
Simmons, Richard L.
Chen, Yue
Schall, Laura
Ford, Henri R.
description 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.
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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. 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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. 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derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>S-nitroso-N-acetyl penicillamine</subject><subject>S-Nitroso-N-Acetylpenicillamine</subject><subject>Superoxide Dismutase - metabolism</subject><subject>thymus</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - drug effects</subject><subject>Thymus Gland - metabolism</subject><subject>Tumor Suppressor Protein p53 - biosynthesis</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1v1DAQBmALgehSOHGvfEC9oGzHayd2jqUqtNWqXOBsOfaE9SpftRNC_j1ud1Fv9OQ5PPOO_BLykcGaMVVe7JtqLdO8VvIVWbGSq4wXkr8mK5CCZbkAOCHvYtwDAN8U8JacMCZ4LkpYEXPvx-At7f94h9R3brIYaTsF3yEdd0vb22VEaoZ-GPvoI62WJ2tG__vR76ewUNM5auiQ88zhgJ3DbqQt2p3pfGzfkze1aSJ-OL6n5OfX6x9XN9n2-7fbq8ttZrkqZCbywiDYXFjDa6OYRaWqelPWuVBKJWPzNFbS2bIQIv3bFQUgsqrC2rHC8lNyfsgdQv8wYRx166PFpjEd9lPUEsq8FAxehEyBVEKJBD8foA19jAFrPQTfmrBoBvqxep2qT7maaSWTPjvGTlWL7tkeu04ADmD2DS7_y9J32y8AT5mfDis7_2s3-4A6tqZp0oWNnuf53-m_2Kicog</recordid><startdate>200107</startdate><enddate>200107</enddate><creator>Gordon, Sherilyn A.</creator><creator>Abou‐Jaoude, Walid</creator><creator>Hoffman, Rosemary A.</creator><creator>McCarthy, Susan A.</creator><creator>Kim, Young‐Myeong</creator><creator>Zhou, Xin</creator><creator>Zhang, Xiao‐Ru</creator><creator>Simmons, Richard L.</creator><creator>Chen, Yue</creator><creator>Schall, Laura</creator><creator>Ford, Henri R.</creator><general>Society for Leukocyte Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200107</creationdate><title>Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism</title><author>Gordon, Sherilyn A. ; 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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.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>11435490</pmid><doi>10.1189/jlb.70.1.87</doi><tpages>9</tpages></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current)
subjects Animals
Apoptosis - drug effects
Apoptosis - physiology
bax
bcl-2-Associated X Protein
catalase
Catalase - metabolism
Coculture Techniques
Enzyme Induction - drug effects
Erythrocytes - cytology
Gene Expression - drug effects
glutathione
Glutathione - metabolism
Heme - metabolism
heme oxygenase
Heme Oxygenase (Decyclizing) - biosynthesis
Heme Oxygenase-1
Iron - metabolism
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Knockout
nitric oxide
Nitric Oxide - pharmacology
Nitric Oxide Donors - pharmacology
Oxidative Stress - drug effects
Oxidative Stress - physiology
p53 protein
Penicillamine - analogs & derivatives
Penicillamine - pharmacology
Proto-Oncogene Proteins - biosynthesis
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - genetics
S-nitroso-N-acetyl penicillamine
S-Nitroso-N-Acetylpenicillamine
Superoxide Dismutase - metabolism
thymus
Thymus Gland - cytology
Thymus Gland - drug effects
Thymus Gland - metabolism
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - physiology
title Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism
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