Eintrag weiter verarbeiten
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells
Gespeichert in:
| Zeitschriftentitel: | International Journal of Molecular Sciences |
|---|---|
| Personen und Körperschaften: | , , |
| In: | International Journal of Molecular Sciences, 20, 2019, 5, S. 1218 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
MDPI AG
|
| Schlagwörter: |
| author_facet |
Tang, Fan Zhang, Rui Wang, Jun Tang, Fan Zhang, Rui Wang, Jun |
|---|---|
| author |
Tang, Fan Zhang, Rui Wang, Jun |
| spellingShingle |
Tang, Fan Zhang, Rui Wang, Jun International Journal of Molecular Sciences Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| author_sort |
tang, fan |
| spelling |
Tang, Fan Zhang, Rui Wang, Jun 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms20051218 <jats:p>Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, and it is a candidate target for sensitizing tumor during therapy. Previous studies identified that increased TFAM expression conferred tumor cells resistance to ionizing radiation. However, the mechanisms on how TFAM are regulated in irradiated tumor cells remain to be explored. In this research, we demonstrated the contribution of cyclooxygenase-2 (COX-2) to enhancing TFAM expression in irradiated tumor cells. Our results showed TFAM was concomitantly up-regulated with COX-2 in irradiated tumor cells. Inhibition of COX-2 by NS-398 blocked radiation-induced expression of TFAM, and prostaglandin E2 (PGE2) treatment stimulated TFAM expression. We next provided evidence that DRP1-mediated mitochondrial fragmentation was a reason for TFAM up-regulation in irradiated cells, by using small interfering RNA (siRNA) and selective inhibitor-targeted DRP1. Furthermore, we proved that p38-MAPK-connected COX-2, and DRP1-mediated TFAM up-regulation. Enhanced phosphorylation of p38 in irradiated tumor cells promoted DRP1 expression, mitochondrial fragmentation, and TFAM expression. NS-398 treatment inhibited radiation-induced p38 phosphorylation, while PGE2 stimulated the activation of p38. The results put forward a mechanism where COX-2 stimulates TFAM expression via p38-mediated DRP1/mitochondrial fragmentation signaling in irradiated tumor cells, which may be of value in understanding how to sensitize cancer cells during radiotherapy.</jats:p> Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells International Journal of Molecular Sciences |
| doi_str_mv |
10.3390/ijms20051218 |
| facet_avail |
Online Free |
| finc_class_facet |
Chemie und Pharmazie Physik Informatik Biologie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMzM5MC9pam1zMjAwNTEyMTg |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMzM5MC9pam1zMjAwNTEyMTg |
| institution |
DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-D161 DE-Zwi2 |
| imprint |
MDPI AG, 2019 |
| imprint_str_mv |
MDPI AG, 2019 |
| issn |
1422-0067 |
| issn_str_mv |
1422-0067 |
| language |
English |
| mega_collection |
MDPI AG (CrossRef) |
| match_str |
tang2019cyclooxygenase2mediatedupregulationofmitochondrialtranscriptionfactoramitigatestheradiosensitivityofcancercells |
| publishDateSort |
2019 |
| publisher |
MDPI AG |
| recordtype |
ai |
| record_format |
ai |
| series |
International Journal of Molecular Sciences |
| source_id |
49 |
| title |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_unstemmed |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_full |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_fullStr |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_full_unstemmed |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_short |
Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_sort |
cyclooxygenase-2-mediated up-regulation of mitochondrial transcription factor a mitigates the radio-sensitivity of cancer cells |
| topic |
Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| url |
http://dx.doi.org/10.3390/ijms20051218 |
| publishDate |
2019 |
| physical |
1218 |
| description |
<jats:p>Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, and it is a candidate target for sensitizing tumor during therapy. Previous studies identified that increased TFAM expression conferred tumor cells resistance to ionizing radiation. However, the mechanisms on how TFAM are regulated in irradiated tumor cells remain to be explored. In this research, we demonstrated the contribution of cyclooxygenase-2 (COX-2) to enhancing TFAM expression in irradiated tumor cells. Our results showed TFAM was concomitantly up-regulated with COX-2 in irradiated tumor cells. Inhibition of COX-2 by NS-398 blocked radiation-induced expression of TFAM, and prostaglandin E2 (PGE2) treatment stimulated TFAM expression. We next provided evidence that DRP1-mediated mitochondrial fragmentation was a reason for TFAM up-regulation in irradiated cells, by using small interfering RNA (siRNA) and selective inhibitor-targeted DRP1. Furthermore, we proved that p38-MAPK-connected COX-2, and DRP1-mediated TFAM up-regulation. Enhanced phosphorylation of p38 in irradiated tumor cells promoted DRP1 expression, mitochondrial fragmentation, and TFAM expression. NS-398 treatment inhibited radiation-induced p38 phosphorylation, while PGE2 stimulated the activation of p38. The results put forward a mechanism where COX-2 stimulates TFAM expression via p38-mediated DRP1/mitochondrial fragmentation signaling in irradiated tumor cells, which may be of value in understanding how to sensitize cancer cells during radiotherapy.</jats:p> |
| container_issue |
5 |
| container_start_page |
0 |
| container_title |
International Journal of Molecular Sciences |
| container_volume |
20 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792333619904118795 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T14:15:14.645Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Cyclooxygenase-2-Mediated+Up-Regulation+of+Mitochondrial+Transcription+Factor+A+Mitigates+the+Radio-Sensitivity+of+Cancer+Cells&rft.date=2019-03-11&genre=article&issn=1422-0067&volume=20&issue=5&pages=1218&jtitle=International+Journal+of+Molecular+Sciences&atitle=Cyclooxygenase-2-Mediated+Up-Regulation+of+Mitochondrial+Transcription+Factor+A+Mitigates+the+Radio-Sensitivity+of+Cancer+Cells&aulast=Wang&aufirst=Jun&rft_id=info%3Adoi%2F10.3390%2Fijms20051218&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792333619904118795 |
| author | Tang, Fan, Zhang, Rui, Wang, Jun |
| author_facet | Tang, Fan, Zhang, Rui, Wang, Jun, Tang, Fan, Zhang, Rui, Wang, Jun |
| author_sort | tang, fan |
| container_issue | 5 |
| container_start_page | 0 |
| container_title | International Journal of Molecular Sciences |
| container_volume | 20 |
| description | <jats:p>Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, and it is a candidate target for sensitizing tumor during therapy. Previous studies identified that increased TFAM expression conferred tumor cells resistance to ionizing radiation. However, the mechanisms on how TFAM are regulated in irradiated tumor cells remain to be explored. In this research, we demonstrated the contribution of cyclooxygenase-2 (COX-2) to enhancing TFAM expression in irradiated tumor cells. Our results showed TFAM was concomitantly up-regulated with COX-2 in irradiated tumor cells. Inhibition of COX-2 by NS-398 blocked radiation-induced expression of TFAM, and prostaglandin E2 (PGE2) treatment stimulated TFAM expression. We next provided evidence that DRP1-mediated mitochondrial fragmentation was a reason for TFAM up-regulation in irradiated cells, by using small interfering RNA (siRNA) and selective inhibitor-targeted DRP1. Furthermore, we proved that p38-MAPK-connected COX-2, and DRP1-mediated TFAM up-regulation. Enhanced phosphorylation of p38 in irradiated tumor cells promoted DRP1 expression, mitochondrial fragmentation, and TFAM expression. NS-398 treatment inhibited radiation-induced p38 phosphorylation, while PGE2 stimulated the activation of p38. The results put forward a mechanism where COX-2 stimulates TFAM expression via p38-mediated DRP1/mitochondrial fragmentation signaling in irradiated tumor cells, which may be of value in understanding how to sensitize cancer cells during radiotherapy.</jats:p> |
| doi_str_mv | 10.3390/ijms20051218 |
| facet_avail | Online, Free |
| finc_class_facet | Chemie und Pharmazie, Physik, Informatik, Biologie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMzM5MC9pam1zMjAwNTEyMTg |
| imprint | MDPI AG, 2019 |
| imprint_str_mv | MDPI AG, 2019 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2 |
| issn | 1422-0067 |
| issn_str_mv | 1422-0067 |
| language | English |
| last_indexed | 2024-03-01T14:15:14.645Z |
| match_str | tang2019cyclooxygenase2mediatedupregulationofmitochondrialtranscriptionfactoramitigatestheradiosensitivityofcancercells |
| mega_collection | MDPI AG (CrossRef) |
| physical | 1218 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | MDPI AG |
| record_format | ai |
| recordtype | ai |
| series | International Journal of Molecular Sciences |
| source_id | 49 |
| spelling | Tang, Fan Zhang, Rui Wang, Jun 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms20051218 <jats:p>Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, and it is a candidate target for sensitizing tumor during therapy. Previous studies identified that increased TFAM expression conferred tumor cells resistance to ionizing radiation. However, the mechanisms on how TFAM are regulated in irradiated tumor cells remain to be explored. In this research, we demonstrated the contribution of cyclooxygenase-2 (COX-2) to enhancing TFAM expression in irradiated tumor cells. Our results showed TFAM was concomitantly up-regulated with COX-2 in irradiated tumor cells. Inhibition of COX-2 by NS-398 blocked radiation-induced expression of TFAM, and prostaglandin E2 (PGE2) treatment stimulated TFAM expression. We next provided evidence that DRP1-mediated mitochondrial fragmentation was a reason for TFAM up-regulation in irradiated cells, by using small interfering RNA (siRNA) and selective inhibitor-targeted DRP1. Furthermore, we proved that p38-MAPK-connected COX-2, and DRP1-mediated TFAM up-regulation. Enhanced phosphorylation of p38 in irradiated tumor cells promoted DRP1 expression, mitochondrial fragmentation, and TFAM expression. NS-398 treatment inhibited radiation-induced p38 phosphorylation, while PGE2 stimulated the activation of p38. The results put forward a mechanism where COX-2 stimulates TFAM expression via p38-mediated DRP1/mitochondrial fragmentation signaling in irradiated tumor cells, which may be of value in understanding how to sensitize cancer cells during radiotherapy.</jats:p> Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells International Journal of Molecular Sciences |
| spellingShingle | Tang, Fan, Zhang, Rui, Wang, Jun, International Journal of Molecular Sciences, Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| title | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_full | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_fullStr | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_full_unstemmed | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_short | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| title_sort | cyclooxygenase-2-mediated up-regulation of mitochondrial transcription factor a mitigates the radio-sensitivity of cancer cells |
| title_unstemmed | Cyclooxygenase-2-Mediated Up-Regulation of Mitochondrial Transcription Factor A Mitigates the Radio-Sensitivity of Cancer Cells |
| topic | Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| url | http://dx.doi.org/10.3390/ijms20051218 |