EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes
Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) plays an important role in DNA damage repair, but its role in RIHD...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-08-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024130 |
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| _version_ | 1841525850405601280 |
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| author | Yu Kaiwen Su Xi Zhou Tongfang Cai Xuwei Zhang Min |
| author_facet | Yu Kaiwen Su Xi Zhou Tongfang Cai Xuwei Zhang Min |
| author_sort | Yu Kaiwen |
| collection | DOAJ |
| description | Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) plays an important role in DNA damage repair, but its role in RIHD is less known. In this study, EEPD1 global knockout mice, C57BL/6J mice, and C57BL/6J mice overexpressing EEPD1 are treated with radiation at a total dose of <sc>20 Gy</sc> or <sc>0 Gy.</sc> After 9 weeks, echocardiography is used to assess cardiac hypertrophy and apoptosis. The results show that EEPD1 deletion exacerbates radiation-induced cardiac hypertrophy and apoptosis, while EEPD1 overexpression has the opposite effect. Further mechanistic investigations reveal that EEPD1 interacts with FOXO3A and destabilizes it by catalyzing its deubiquitination. Inhibition of FOXO3A ameliorates cardiac hypertrophy and apoptosis after EEPD1 knockdown. Thus, EEPD1 protects against radiation-induced cardiac hypertrophy and apoptosis via destabilization of FOXO3A, which may offer new insight into therapeutic strategies for RIHD. |
| format | Article |
| id | doaj-art-6a42eae959964cefb193093b460a6179 |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-6a42eae959964cefb193093b460a61792025-01-17T05:58:28ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-08-01561733174710.3724/abbs.202413020d259ccEEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytesYu Kaiwen0Su Xi1Zhou Tongfang2Cai Xuwei3Zhang Min4["Department of Cardiology, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China"]["Department of Cardiology, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China"]["Radiotherapy Department of Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China"]["Department of Cardiology, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China"]["Department of Cardiology, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China"]Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) plays an important role in DNA damage repair, but its role in RIHD is less known. In this study, EEPD1 global knockout mice, C57BL/6J mice, and C57BL/6J mice overexpressing EEPD1 are treated with radiation at a total dose of <sc>20 Gy</sc> or <sc>0 Gy.</sc> After 9 weeks, echocardiography is used to assess cardiac hypertrophy and apoptosis. The results show that EEPD1 deletion exacerbates radiation-induced cardiac hypertrophy and apoptosis, while EEPD1 overexpression has the opposite effect. Further mechanistic investigations reveal that EEPD1 interacts with FOXO3A and destabilizes it by catalyzing its deubiquitination. Inhibition of FOXO3A ameliorates cardiac hypertrophy and apoptosis after EEPD1 knockdown. Thus, EEPD1 protects against radiation-induced cardiac hypertrophy and apoptosis via destabilization of FOXO3A, which may offer new insight into therapeutic strategies for RIHD.https://www.sciengine.com/doi/10.3724/abbs.2024130<italic>EEPD1</italic>radiation-induced heart diseasecardiac hypertrophyapoptosis<italic>FOXO3A</italic> |
| spellingShingle | Yu Kaiwen Su Xi Zhou Tongfang Cai Xuwei Zhang Min EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes Acta Biochimica et Biophysica Sinica <italic>EEPD1</italic> radiation-induced heart disease cardiac hypertrophy apoptosis <italic>FOXO3A</italic> |
| title | EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes |
| title_full | EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes |
| title_fullStr | EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes |
| title_full_unstemmed | EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes |
| title_short | EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes |
| title_sort | eepd1 attenuates radiation induced cardiac hypertrophy and apoptosis by degrading foxo3a in cardiomyocytes |
| topic | <italic>EEPD1</italic> radiation-induced heart disease cardiac hypertrophy apoptosis <italic>FOXO3A</italic> |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024130 |
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