Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells
HDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of...
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| Format: | Article |
| Language: | English |
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AIMS Press
2018-02-01
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| Series: | AIMS Genetics |
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| Online Access: | http://www.aimspress.com/Genetics/article/1825/fulltext.html |
| _version_ | 1819060486184894464 |
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| author | Alisa Morshneva Olga Gnedina Svetlana Svetlikova Valery Pospelov Maria Igotti |
| author_facet | Alisa Morshneva Olga Gnedina Svetlana Svetlikova Valery Pospelov Maria Igotti |
| author_sort | Alisa Morshneva |
| collection | DOAJ |
| description | HDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. It’s known that HDACs regulate the ROS-dependent FoxO factors, which are responsible for cell growth, proliferation, and longevity. The characteristic ROS increase during aging may be responsible for the decreased HDAC activity, which facilitates the senescent-like phenotype. The objective of this study was to investigate the impact of FoxO transcription factors on HDACIs-induced senescence of E1A+Ras oncogenes transformed cells. This study shows the specific time-dependent effect of HDACI sodium butyrate treatment on FoxO proteins in E1A+Ras cells. Indeed, short-term treatment with NaB results in FoxO activation, which takes place through nuclear translocation, and accompanied by accumulation of such ROS scavengers as MnSOD and SOD2. However, prolonged treatment leads to extensive FoxO degradation and increased intracellular levels of ROS. This degradation is connected with NaB-induced activation of Akt kinase. All of these findings establish that one of the possible mechanism involved in NaB-induced senescence of transformed cells is mediated through down-regulation of FoxO transcription factors and ROS accumulation. |
| first_indexed | 2024-12-21T14:27:45Z |
| format | Article |
| id | doaj.art-6f4a2bb4156a4187a23a44a418cd7504 |
| institution | Directory Open Access Journal |
| issn | 2377-1143 |
| language | English |
| last_indexed | 2024-12-21T14:27:45Z |
| publishDate | 2018-02-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | AIMS Genetics |
| spelling | doaj.art-6f4a2bb4156a4187a23a44a418cd75042022-12-21T19:00:35ZengAIMS PressAIMS Genetics2377-11432018-02-0151415210.3934/genet.2018.1.41genetics-05-00041Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cellsAlisa Morshneva0Olga Gnedina1Svetlana Svetlikova2Valery Pospelov3Maria Igotti4Institute of Cytology, Russian Academy of Sciences, St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St. Petersburg, RussiaHDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. It’s known that HDACs regulate the ROS-dependent FoxO factors, which are responsible for cell growth, proliferation, and longevity. The characteristic ROS increase during aging may be responsible for the decreased HDAC activity, which facilitates the senescent-like phenotype. The objective of this study was to investigate the impact of FoxO transcription factors on HDACIs-induced senescence of E1A+Ras oncogenes transformed cells. This study shows the specific time-dependent effect of HDACI sodium butyrate treatment on FoxO proteins in E1A+Ras cells. Indeed, short-term treatment with NaB results in FoxO activation, which takes place through nuclear translocation, and accompanied by accumulation of such ROS scavengers as MnSOD and SOD2. However, prolonged treatment leads to extensive FoxO degradation and increased intracellular levels of ROS. This degradation is connected with NaB-induced activation of Akt kinase. All of these findings establish that one of the possible mechanism involved in NaB-induced senescence of transformed cells is mediated through down-regulation of FoxO transcription factors and ROS accumulation.http://www.aimspress.com/Genetics/article/1825/fulltext.htmlhistone deacetylase inhibitor (HDACi)sodium butyrateFoxOoxidative stressROSAktnuclear shuttling |
| spellingShingle | Alisa Morshneva Olga Gnedina Svetlana Svetlikova Valery Pospelov Maria Igotti Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells AIMS Genetics histone deacetylase inhibitor (HDACi) sodium butyrate FoxO oxidative stress ROS Akt nuclear shuttling |
| title | Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells |
| title_full | Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells |
| title_fullStr | Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells |
| title_full_unstemmed | Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells |
| title_short | Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells |
| title_sort | time dependent modulation of foxo activity by hdac inhibitor in oncogene transformed e1a ras cells |
| topic | histone deacetylase inhibitor (HDACi) sodium butyrate FoxO oxidative stress ROS Akt nuclear shuttling |
| url | http://www.aimspress.com/Genetics/article/1825/fulltext.html |
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