New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo
Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 a...
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description | Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that the peptide up-regulation of all three enzymes appears to be a coordinated process which occurs in vitro and in vivo. We also found that ischemia alone, without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX. This suggests that the CNS can initiate its own “defense” against ROS and FR. Thus, our peptides may activate such systems, as well as AP-1 transcription factor, reported in earlier findings to lead to “repair” (growth) of injured cells. |
doi_str_mv | 10.1016/j.brainres.2004.06.086 |
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Miscellaneous ; Neurodegenerative disease ; Neurology ; Peptide effect ; Peptides - pharmacology ; Rats ; Superoxide dismutase ; Superoxide Dismutase - biosynthesis ; Superoxide Dismutase - genetics ; Up-regulation of antioxidant genes</subject><ispartof>Brain research, 2004-10, Vol.1024 (1), p.34-43</ispartof><rights>2004 Elsevier B.V.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-8f526419bb4024bd65f2c5262824033f49890df760e5c840ee6284a5a47b7dd03</citedby><cites>FETCH-LOGICAL-c460t-8f526419bb4024bd65f2c5262824033f49890df760e5c840ee6284a5a47b7dd03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2004.06.086$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16158887$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15451365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shashoua, Victor E.</creatorcontrib><creatorcontrib>Adams, David S.</creatorcontrib><creatorcontrib>Volodina, Natalia V.</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><title>New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that the peptide up-regulation of all three enzymes appears to be a coordinated process which occurs in vitro and in vivo. We also found that ischemia alone, without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX. This suggests that the CNS can initiate its own “defense” against ROS and FR. Thus, our peptides may activate such systems, as well as AP-1 transcription factor, reported in earlier findings to lead to “repair” (growth) of injured cells.</description><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>AP-1 transcription factor</subject><subject>Biological and medical sciences</subject><subject>Catalase</subject><subject>Catalase - biosynthesis</subject><subject>Catalase - genetics</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - enzymology</subject><subject>Ependymin</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Gene Expression Regulation, Enzymologic - physiology</subject><subject>Glutathione peroxidase</subject><subject>Glutathione Peroxidase - biosynthesis</subject><subject>Glutathione Peroxidase - genetics</subject><subject>Ischemia effect</subject><subject>Medical sciences</subject><subject>Nervous system involvement in other diseases. Miscellaneous</subject><subject>Neurodegenerative disease</subject><subject>Neurology</subject><subject>Peptide effect</subject><subject>Peptides - pharmacology</subject><subject>Rats</subject><subject>Superoxide dismutase</subject><subject>Superoxide Dismutase - biosynthesis</subject><subject>Superoxide Dismutase - genetics</subject><subject>Up-regulation of antioxidant genes</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v3CAQhlHVqNmm_QsRl_Zmd7AB41urKP2QoubSnhGGoWG7Cy54t9n8-hDtVjn2NBp4XmZ4CLlk0DJg8sO6nbIJMWNpOwDegmxByRdkxdTQNbLj8JKsAEA2ahz7c_K6lHVt-36EV-ScCS5YL8WKrL_jX1oOcbnDJVg647wEh4VaEynGOxMt0l8YkeL9XIeVkCJNnv7GAzVxCek-uFqpQ4-xVCo-HLY1HiLdhyWnCrljs09vyJk3m4JvT_WC_Px8_ePqa3Nz--Xb1aebxnIJS6O86CRn4zRx6PjkpPCdrUedqp_qe89HNYLzgwQUVnFArFfcCMOHaXAO-gvy_vjunNOfHZZFb0OxuNmYiGlXNBu4ErxnFZRH0OZUSkav5xy2Jh80A_1kWa_1P8v6ybIGqavlGrw8TdhNW3TPsZPWCrw7AaZYs_G5egzlmZNMKKWGyn08clh97ANmXWzA6tyFjHbRLoX_7fIICT-fJw</recordid><startdate>20041022</startdate><enddate>20041022</enddate><creator>Shashoua, Victor E.</creator><creator>Adams, David S.</creator><creator>Volodina, Natalia V.</creator><creator>Li, Hua</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7TK</scope></search><sort><creationdate>20041022</creationdate><title>New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo</title><author>Shashoua, Victor E. ; Adams, David S. ; Volodina, Natalia V. ; Li, Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-8f526419bb4024bd65f2c5262824033f49890df760e5c840ee6284a5a47b7dd03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>AP-1 transcription factor</topic><topic>Biological and medical sciences</topic><topic>Catalase</topic><topic>Catalase - biosynthesis</topic><topic>Catalase - genetics</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - enzymology</topic><topic>Ependymin</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Gene Expression Regulation, Enzymologic - physiology</topic><topic>Glutathione peroxidase</topic><topic>Glutathione Peroxidase - biosynthesis</topic><topic>Glutathione Peroxidase - genetics</topic><topic>Ischemia effect</topic><topic>Medical sciences</topic><topic>Nervous system involvement in other diseases. Miscellaneous</topic><topic>Neurodegenerative disease</topic><topic>Neurology</topic><topic>Peptide effect</topic><topic>Peptides - pharmacology</topic><topic>Rats</topic><topic>Superoxide dismutase</topic><topic>Superoxide Dismutase - biosynthesis</topic><topic>Superoxide Dismutase - genetics</topic><topic>Up-regulation of antioxidant genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shashoua, Victor E.</creatorcontrib><creatorcontrib>Adams, David S.</creatorcontrib><creatorcontrib>Volodina, Natalia V.</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><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>Neurosciences Abstracts</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shashoua, Victor E.</au><au>Adams, David S.</au><au>Volodina, Natalia V.</au><au>Li, Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2004-10-22</date><risdate>2004</risdate><volume>1024</volume><issue>1</issue><spage>34</spage><epage>43</epage><pages>34-43</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that the peptide up-regulation of all three enzymes appears to be a coordinated process which occurs in vitro and in vivo. We also found that ischemia alone, without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX. This suggests that the CNS can initiate its own “defense” against ROS and FR. 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subjects | Animals Antioxidants - metabolism AP-1 transcription factor Biological and medical sciences Catalase Catalase - biosynthesis Catalase - genetics Cells, Cultured Cerebral Cortex - drug effects Cerebral Cortex - enzymology Ependymin Gene Expression Regulation, Enzymologic - drug effects Gene Expression Regulation, Enzymologic - physiology Glutathione peroxidase Glutathione Peroxidase - biosynthesis Glutathione Peroxidase - genetics Ischemia effect Medical sciences Nervous system involvement in other diseases. Miscellaneous Neurodegenerative disease Neurology Peptide effect Peptides - pharmacology Rats Superoxide dismutase Superoxide Dismutase - biosynthesis Superoxide Dismutase - genetics Up-regulation of antioxidant genes |
title | New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo |
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