Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts
The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcri...
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| Veröffentlicht in: | Genomics (San Diego, Calif.) Calif.), 2012-11, Vol.100 (5), p.277-281 |
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| creator | Sokolov, Mykyta V. Panyutin, Igor G. Neumann, Ronald D. |
| description | The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways.
► Effect of NO depletion on transcriptome changes in human cells post-IR is studied. ► More than seven-fold reduction of the number of upregulated genes after IR observed. ► NO scavenging in IR fibroblasts induces p53 signaling, DNA damage/repair pathways. ► Involvement of ROS in transcriptional response of irradiated cells is also examined. |
| doi_str_mv | 10.1016/j.ygeno.2012.07.007 |
| format | Article |
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► Effect of NO depletion on transcriptome changes in human cells post-IR is studied. ► More than seven-fold reduction of the number of upregulated genes after IR observed. ► NO scavenging in IR fibroblasts induces p53 signaling, DNA damage/repair pathways. ► Involvement of ROS in transcriptional response of irradiated cells is also examined.</description><identifier>ISSN: 0888-7543</identifier><identifier>EISSN: 1089-8646</identifier><identifier>DOI: 10.1016/j.ygeno.2012.07.007</identifier><identifier>PMID: 22814268</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Benzoates ; Biological and medical sciences ; Cell culture ; Cell Line ; Data processing ; Dimethyl Sulfoxide ; DNA damage ; DNA microarray ; DNA repair ; Fibroblasts ; Free Radical Scavengers - metabolism ; Fundamental and applied biological sciences. Psychology ; gamma radiation ; Gamma Rays ; Gene expression ; Gene Expression Profiling - methods ; gene expression regulation ; Gene Expression Regulation - radiation effects ; genes ; Genes. Genome ; Genetics of eukaryotes. Biological and molecular evolution ; Genome, Human - genetics ; Humans ; Imidazoles ; Ionizing radiation ; irradiation ; Molecular and cellular biology ; Molecular genetics ; Nitric oxide ; Nitric Oxide - metabolism ; Nitrogen ; Normal human fibroblast ; Oligonucleotide Array Sequence Analysis ; Oxygen ; p53 protein ; Reactive oxygen species ; Signal transduction ; Transcription ; transcription (genetics) ; Transcription, Genetic - physiology ; Transcription, Genetic - radiation effects ; Transcription. Transcription factor. Splicing. Rna processing ; transcriptome</subject><ispartof>Genomics (San Diego, Calif.), 2012-11, Vol.100 (5), p.277-281</ispartof><rights>2012</rights><rights>2014 INIST-CNRS</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-9f46c848fcd9979d1391336deb43cb0ea9e5052c465277c2420dff4f1455cfea3</citedby><cites>FETCH-LOGICAL-c546t-9f46c848fcd9979d1391336deb43cb0ea9e5052c465277c2420dff4f1455cfea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ygeno.2012.07.007$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26674525$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22814268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sokolov, Mykyta V.</creatorcontrib><creatorcontrib>Panyutin, Igor G.</creatorcontrib><creatorcontrib>Neumann, Ronald D.</creatorcontrib><title>Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts</title><title>Genomics (San Diego, Calif.)</title><addtitle>Genomics</addtitle><description>The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways.
► Effect of NO depletion on transcriptome changes in human cells post-IR is studied. ► More than seven-fold reduction of the number of upregulated genes after IR observed. ► NO scavenging in IR fibroblasts induces p53 signaling, DNA damage/repair pathways. ► Involvement of ROS in transcriptional response of irradiated cells is also examined.</description><subject>Benzoates</subject><subject>Biological and medical sciences</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Data processing</subject><subject>Dimethyl Sulfoxide</subject><subject>DNA damage</subject><subject>DNA microarray</subject><subject>DNA repair</subject><subject>Fibroblasts</subject><subject>Free Radical Scavengers - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gamma radiation</subject><subject>Gamma Rays</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>gene expression regulation</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>genes</subject><subject>Genes. Genome</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome, Human - genetics</subject><subject>Humans</subject><subject>Imidazoles</subject><subject>Ionizing radiation</subject><subject>irradiation</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitrogen</subject><subject>Normal human fibroblast</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oxygen</subject><subject>p53 protein</subject><subject>Reactive oxygen species</subject><subject>Signal transduction</subject><subject>Transcription</subject><subject>transcription (genetics)</subject><subject>Transcription, Genetic - physiology</subject><subject>Transcription, Genetic - radiation effects</subject><subject>Transcription. Transcription factor. Splicing. Rna processing</subject><subject>transcriptome</subject><issn>0888-7543</issn><issn>1089-8646</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks-O0zAQxiMEYsvCEyCBL0hcUmzHcZwDK6EV_6SVOMCKo-U649ZVYgc7rXZ5LJ6QSVsWuCBOluzf982M5yuKp4wuGWXy1XZ5u4YQl5wyvqTNktLmXrFgVLWlkkLeLxZUKVU2tajOikc5bymlbaX4w-KMc8UEl2pR_Pi6iT2Us9EABA8gcDMmyNnHQMYUne99WJMEezB9JtMGyGC2MZGEOhIdCX5K3pJ44zsgPpABOm-mWTOzFvp-15tEpmRCtsmPExqbHg3zGEMGMkWCN_77oYo5aLEyGoWYBgQ3u8EE4vwqxVVv8pQfFw8ctgJPTud5cf3u7ZfLD-XVp_cfL99clbYWcipbJ6RVQjnbtW3TdqxqWVXJDlaisisKpoWa1twKWfOmsVxw2jknHBN1bR2Y6ry4OPqOuxUOZSHgDL0ekx9MutXReP33S_AbvY57XQlVCUbR4OXJIMVvO8iTHnyeP8QEiLusGWuYahGV_4FyLiteyxmtjqhNMecE7q4jRvUcDL3Vh2DoORiaNhqDgapnfw5zp_mVBARenACTrekdrsv6_JuTshE1r5F7fuScidqsEzLXn7FSjekSnEmOxOsjAbicvYeks_UQLOYigZ10F_0_W_0JS5TnGA</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>Sokolov, Mykyta V.</creator><creator>Panyutin, Igor G.</creator><creator>Neumann, Ronald D.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>IQODW</scope><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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121101</creationdate><title>Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts</title><author>Sokolov, Mykyta V. ; Panyutin, Igor G. ; Neumann, Ronald D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-9f46c848fcd9979d1391336deb43cb0ea9e5052c465277c2420dff4f1455cfea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Benzoates</topic><topic>Biological and medical sciences</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Data processing</topic><topic>Dimethyl Sulfoxide</topic><topic>DNA damage</topic><topic>DNA microarray</topic><topic>DNA repair</topic><topic>Fibroblasts</topic><topic>Free Radical Scavengers - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gamma radiation</topic><topic>Gamma Rays</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>gene expression regulation</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>genes</topic><topic>Genes. Genome</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome, Human - genetics</topic><topic>Humans</topic><topic>Imidazoles</topic><topic>Ionizing radiation</topic><topic>irradiation</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitrogen</topic><topic>Normal human fibroblast</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oxygen</topic><topic>p53 protein</topic><topic>Reactive oxygen species</topic><topic>Signal transduction</topic><topic>Transcription</topic><topic>transcription (genetics)</topic><topic>Transcription, Genetic - physiology</topic><topic>Transcription, Genetic - radiation effects</topic><topic>Transcription. Transcription factor. Splicing. Rna processing</topic><topic>transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sokolov, Mykyta V.</creatorcontrib><creatorcontrib>Panyutin, Igor G.</creatorcontrib><creatorcontrib>Neumann, Ronald D.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genomics (San Diego, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sokolov, Mykyta V.</au><au>Panyutin, Igor G.</au><au>Neumann, Ronald D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts</atitle><jtitle>Genomics (San Diego, Calif.)</jtitle><addtitle>Genomics</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>100</volume><issue>5</issue><spage>277</spage><epage>281</epage><pages>277-281</pages><issn>0888-7543</issn><eissn>1089-8646</eissn><abstract>The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways.
► Effect of NO depletion on transcriptome changes in human cells post-IR is studied. ► More than seven-fold reduction of the number of upregulated genes after IR observed. ► NO scavenging in IR fibroblasts induces p53 signaling, DNA damage/repair pathways. ► Involvement of ROS in transcriptional response of irradiated cells is also examined.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22814268</pmid><doi>10.1016/j.ygeno.2012.07.007</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Benzoates Biological and medical sciences Cell culture Cell Line Data processing Dimethyl Sulfoxide DNA damage DNA microarray DNA repair Fibroblasts Free Radical Scavengers - metabolism Fundamental and applied biological sciences. Psychology gamma radiation Gamma Rays Gene expression Gene Expression Profiling - methods gene expression regulation Gene Expression Regulation - radiation effects genes Genes. Genome Genetics of eukaryotes. Biological and molecular evolution Genome, Human - genetics Humans Imidazoles Ionizing radiation irradiation Molecular and cellular biology Molecular genetics Nitric oxide Nitric Oxide - metabolism Nitrogen Normal human fibroblast Oligonucleotide Array Sequence Analysis Oxygen p53 protein Reactive oxygen species Signal transduction Transcription transcription (genetics) Transcription, Genetic - physiology Transcription, Genetic - radiation effects Transcription. Transcription factor. Splicing. Rna processing transcriptome |
| title | Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts |
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