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Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress
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Veröffentlicht in: | Scientific reports 7(2017) Artikel-Nummer 15388, 11 Seiten |
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Personen und Körperschaften: | , , |
Titel: | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress/ Xinlai Cheng, Christiane Peuckert & Stefan Wölfl |
Format: | E-Book-Kapitel |
Sprache: | Englisch |
veröffentlicht: |
13 November 2017
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Gesamtaufnahme: |
: Scientific reports, 7(2017) Artikel-Nummer 15388, 11 Seiten
, volume:7 |
Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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author | Cheng, Xinlai, Peuckert, Christiane, Wölfl, Stefan |
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contents | Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3Y705 contributes to its nucleic translocation, while phospho-Stat3S727 leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3Y705, little is known about Stat3S727. In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing. We found dysregulation of mitochondrial activity, which was associated with excessive ROS formation and reduced mitochondrial membrane potential, and observed a synergistic effect for oxidative stress-mediated apoptosis in Stat3-KD cells or cells carrying Stat3Y705F, but not Stat3S727D, suggesting the importance of functional mitochondrial Stat3 in this context. We also found that ROS-mediated activation of ASK1/p38MAPK was involved and adding antioxidants, p38MAPK inhibitor, or genetic repression of ASK1 could easily rescue the cellular damage. Our finding reveals a new role of mitochondrial Stat3 in preventing ASK1/p38MAPK-mediated apoptosis, wich further support the notion that selective inhibition mitochondrial Stat3 could provide a primsing target for chemotherapy. |
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spelling | Cheng, Xinlai 1978- VerfasserIn (DE-588)140211586 (DE-627)616944179 (DE-576)315074698 aut, Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress Xinlai Cheng, Christiane Peuckert & Stefan Wölfl, Essential role of mitochondrial Stat3 in p38 MAPK mediated apoptosis under oxidative stress, 13 November 2017, 11, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 06.04.2018, MAPK ist im Titel hochgestellt, Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3Y705 contributes to its nucleic translocation, while phospho-Stat3S727 leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3Y705, little is known about Stat3S727. In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing. We found dysregulation of mitochondrial activity, which was associated with excessive ROS formation and reduced mitochondrial membrane potential, and observed a synergistic effect for oxidative stress-mediated apoptosis in Stat3-KD cells or cells carrying Stat3Y705F, but not Stat3S727D, suggesting the importance of functional mitochondrial Stat3 in this context. We also found that ROS-mediated activation of ASK1/p38MAPK was involved and adding antioxidants, p38MAPK inhibitor, or genetic repression of ASK1 could easily rescue the cellular damage. Our finding reveals a new role of mitochondrial Stat3 in preventing ASK1/p38MAPK-mediated apoptosis, wich further support the notion that selective inhibition mitochondrial Stat3 could provide a primsing target for chemotherapy., Peuckert, Christiane 1975- VerfasserIn (DE-588)133318753 (DE-627)540525790 (DE-576)272311375 aut, Wölfl, Stefan 1959- VerfasserIn (DE-588)121047458 (DE-627)081052618 (DE-576)260692360 aut, Enthalten in Scientific reports [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 7(2017) Artikel-Nummer 15388, 11 Seiten Online-Ressource (DE-627)663366712 (DE-600)2615211-3 (DE-576)346641179 2045-2322 nnns, volume:7 year:2017 extent:11, http://dx.doi.org/10.1038/s41598-017-15342-4 Verlag Resolving-System kostenfrei Volltext, https://www.nature.com/articles/s41598-017-15342-4 Verlag kostenfrei Volltext, http://dx.doi.org/10.1038/s41598-017-15342-4 LFER, LFER 2018-05-17T00:00:00Z |
spellingShingle | Cheng, Xinlai, Peuckert, Christiane, Wölfl, Stefan, Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress, Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3Y705 contributes to its nucleic translocation, while phospho-Stat3S727 leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3Y705, little is known about Stat3S727. In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing. We found dysregulation of mitochondrial activity, which was associated with excessive ROS formation and reduced mitochondrial membrane potential, and observed a synergistic effect for oxidative stress-mediated apoptosis in Stat3-KD cells or cells carrying Stat3Y705F, but not Stat3S727D, suggesting the importance of functional mitochondrial Stat3 in this context. We also found that ROS-mediated activation of ASK1/p38MAPK was involved and adding antioxidants, p38MAPK inhibitor, or genetic repression of ASK1 could easily rescue the cellular damage. Our finding reveals a new role of mitochondrial Stat3 in preventing ASK1/p38MAPK-mediated apoptosis, wich further support the notion that selective inhibition mitochondrial Stat3 could provide a primsing target for chemotherapy. |
swb_id_str | 501779523 |
title | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress |
title_alt | Essential role of mitochondrial Stat3 in p38 MAPK mediated apoptosis under oxidative stress |
title_auth | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress |
title_full | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress Xinlai Cheng, Christiane Peuckert & Stefan Wölfl |
title_fullStr | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress Xinlai Cheng, Christiane Peuckert & Stefan Wölfl |
title_full_unstemmed | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress Xinlai Cheng, Christiane Peuckert & Stefan Wölfl |
title_in_hierarchy | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress / Xinlai Cheng, Christiane Peuckert & Stefan Wölfl, |
title_short | Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress |
title_sort | essential role of mitochondrial stat3 in p38mapk mediated apoptosis under oxidative stress |
url | http://dx.doi.org/10.1038/s41598-017-15342-4, https://www.nature.com/articles/s41598-017-15342-4 |