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Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin
BACKGROUND: Homeostasis of reactive oxygen species (ROS) in the skin is regulated by antioxidant defenses. The inflammatory states of skin diseases which range from acute rashes to chronic conditions are related to the level of ROS. The involvement of superoxide dismutase (SOD) in restoring the anti...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719741/ https://www.ncbi.nlm.nih.gov/pubmed/26786970 http://dx.doi.org/10.1186/s12929-016-0226-7 |
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author | Liu, Tsang-Pai Chen, Yi-Ping Chou, Chih-Ming Chiu, Ting-Ting Chen, Chien-Tsu |
author_facet | Liu, Tsang-Pai Chen, Yi-Ping Chou, Chih-Ming Chiu, Ting-Ting Chen, Chien-Tsu |
author_sort | Liu, Tsang-Pai |
collection | PubMed |
description | BACKGROUND: Homeostasis of reactive oxygen species (ROS) in the skin is regulated by antioxidant defenses. The inflammatory states of skin diseases which range from acute rashes to chronic conditions are related to the level of ROS. The involvement of superoxide dismutase (SOD) in restoring the antioxidant capacity can then neutralize the inflammatory response. RESULTS: We found that denatured Tat-SOD formulated in an aqueous medium could be delivered into mouse skin and the penetration signals of Tat-SOD were detected in the epidermis and dermis. According to immunohistochemical staining, Tat-SOD successfully suppressed inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), the expression of sodium nitroferricyanide (SNP)-induced cyclooxygenase-2 (COX-2), and the production of nitrotyrosine proteins. In nerve growth factor (NGF) induced differentiated PC12 pheochromocytoma cells, we demonstrated that the denatured Tat-SOD regained its antioxidant activity and effectively protected PC12 cells from DNA fragmentation induced by paraquat. Using a luciferase reporter assay, the data was shown Tat-SOD protected PC12 cells from ROS damage, through suppression of COX-2 or nuclear factor-κB (NF-κB) activity occurred at the transcriptional level. CONCLUSION: We showed that Tat-SOD inhibited SNP-induced COX-2 expression similarly to celecoxib and prevented the formation of peroxynitrite as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The results suggest that denatured Tat-SOD solution may perform potential protein therapy for patients suffering from disorders related to ROS. |
format | Online Article Text |
id | pubmed-4719741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47197412016-01-21 Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin Liu, Tsang-Pai Chen, Yi-Ping Chou, Chih-Ming Chiu, Ting-Ting Chen, Chien-Tsu J Biomed Sci Research BACKGROUND: Homeostasis of reactive oxygen species (ROS) in the skin is regulated by antioxidant defenses. The inflammatory states of skin diseases which range from acute rashes to chronic conditions are related to the level of ROS. The involvement of superoxide dismutase (SOD) in restoring the antioxidant capacity can then neutralize the inflammatory response. RESULTS: We found that denatured Tat-SOD formulated in an aqueous medium could be delivered into mouse skin and the penetration signals of Tat-SOD were detected in the epidermis and dermis. According to immunohistochemical staining, Tat-SOD successfully suppressed inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), the expression of sodium nitroferricyanide (SNP)-induced cyclooxygenase-2 (COX-2), and the production of nitrotyrosine proteins. In nerve growth factor (NGF) induced differentiated PC12 pheochromocytoma cells, we demonstrated that the denatured Tat-SOD regained its antioxidant activity and effectively protected PC12 cells from DNA fragmentation induced by paraquat. Using a luciferase reporter assay, the data was shown Tat-SOD protected PC12 cells from ROS damage, through suppression of COX-2 or nuclear factor-κB (NF-κB) activity occurred at the transcriptional level. CONCLUSION: We showed that Tat-SOD inhibited SNP-induced COX-2 expression similarly to celecoxib and prevented the formation of peroxynitrite as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The results suggest that denatured Tat-SOD solution may perform potential protein therapy for patients suffering from disorders related to ROS. BioMed Central 2016-01-20 /pmc/articles/PMC4719741/ /pubmed/26786970 http://dx.doi.org/10.1186/s12929-016-0226-7 Text en © Liu et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Liu, Tsang-Pai Chen, Yi-Ping Chou, Chih-Ming Chiu, Ting-Ting Chen, Chien-Tsu Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title | Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title_full | Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title_fullStr | Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title_full_unstemmed | Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title_short | Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin |
title_sort | therapeutic evaluation of hiv transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of cox-2 in murine skin |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719741/ https://www.ncbi.nlm.nih.gov/pubmed/26786970 http://dx.doi.org/10.1186/s12929-016-0226-7 |
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