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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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. |
doi_str_mv | 10.1189/jlb.70.1.87 |
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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. 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.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.70.1.87</identifier><identifier>PMID: 11435490</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>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</subject><ispartof>Journal of leukocyte biology, 2001-07, Vol.70 (1), p.87-95</ispartof><rights>2001 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3867-456ae0c54ca3fa81ce88bf29f54888c38c5f54b7dc9644189d660ee1bbefd16c3</citedby><cites>FETCH-LOGICAL-c3867-456ae0c54ca3fa81ce88bf29f54888c38c5f54b7dc9644189d660ee1bbefd16c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.70.1.87$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.70.1.87$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11435490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gordon, Sherilyn A.</creatorcontrib><creatorcontrib>Abou‐Jaoude, Walid</creatorcontrib><creatorcontrib>Hoffman, Rosemary A.</creatorcontrib><creatorcontrib>McCarthy, Susan A.</creatorcontrib><creatorcontrib>Kim, Young‐Myeong</creatorcontrib><creatorcontrib>Zhou, Xin</creatorcontrib><creatorcontrib>Zhang, Xiao‐Ru</creatorcontrib><creatorcontrib>Simmons, Richard L.</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><creatorcontrib>Schall, Laura</creatorcontrib><creatorcontrib>Ford, Henri R.</creatorcontrib><title>Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><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.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>bax</subject><subject>bcl-2-Associated X Protein</subject><subject>catalase</subject><subject>Catalase - metabolism</subject><subject>Coculture Techniques</subject><subject>Enzyme Induction - drug effects</subject><subject>Erythrocytes - cytology</subject><subject>Gene Expression - drug effects</subject><subject>glutathione</subject><subject>Glutathione - metabolism</subject><subject>Heme - metabolism</subject><subject>heme oxygenase</subject><subject>Heme Oxygenase (Decyclizing) - biosynthesis</subject><subject>Heme Oxygenase-1</subject><subject>Iron - metabolism</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>nitric oxide</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>p53 protein</subject><subject>Penicillamine - analogs & 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. ; 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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3867-456ae0c54ca3fa81ce88bf29f54888c38c5f54b7dc9644189d660ee1bbefd16c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>bax</topic><topic>bcl-2-Associated X Protein</topic><topic>catalase</topic><topic>Catalase - metabolism</topic><topic>Coculture Techniques</topic><topic>Enzyme Induction - drug effects</topic><topic>Erythrocytes - cytology</topic><topic>Gene Expression - drug effects</topic><topic>glutathione</topic><topic>Glutathione - metabolism</topic><topic>Heme - metabolism</topic><topic>heme oxygenase</topic><topic>Heme Oxygenase (Decyclizing) - biosynthesis</topic><topic>Heme Oxygenase-1</topic><topic>Iron - metabolism</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>nitric oxide</topic><topic>Nitric Oxide - pharmacology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>p53 protein</topic><topic>Penicillamine - analogs & derivatives</topic><topic>Penicillamine - pharmacology</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>S-nitroso-N-acetyl penicillamine</topic><topic>S-Nitroso-N-Acetylpenicillamine</topic><topic>Superoxide Dismutase - metabolism</topic><topic>thymus</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - drug effects</topic><topic>Thymus Gland - metabolism</topic><topic>Tumor Suppressor Protein p53 - biosynthesis</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gordon, Sherilyn A.</creatorcontrib><creatorcontrib>Abou‐Jaoude, Walid</creatorcontrib><creatorcontrib>Hoffman, Rosemary A.</creatorcontrib><creatorcontrib>McCarthy, Susan A.</creatorcontrib><creatorcontrib>Kim, Young‐Myeong</creatorcontrib><creatorcontrib>Zhou, Xin</creatorcontrib><creatorcontrib>Zhang, Xiao‐Ru</creatorcontrib><creatorcontrib>Simmons, Richard L.</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><creatorcontrib>Schall, Laura</creatorcontrib><creatorcontrib>Ford, Henri R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gordon, Sherilyn A.</au><au>Abou‐Jaoude, Walid</au><au>Hoffman, Rosemary A.</au><au>McCarthy, Susan A.</au><au>Kim, Young‐Myeong</au><au>Zhou, Xin</au><au>Zhang, Xiao‐Ru</au><au>Simmons, Richard L.</au><au>Chen, Yue</au><au>Schall, Laura</au><au>Ford, Henri R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2001-07</date><risdate>2001</risdate><volume>70</volume><issue>1</issue><spage>87</spage><epage>95</epage><pages>87-95</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>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.</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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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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