EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes

• Published in: Acta biochimica et biophysica Sinica 2024-12, Vol.56 (12), p.1733-1747
• Main Authors: Yu, Kaiwen, Su, Xi, Zhou, Tongfang, Cai, Xuwei, Zhang, Min
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; cardiac hypertrophy; Cardiomegaly - etiology; Cardiomegaly - genetics; Cardiomegaly - metabolism; EEPD1; Forkhead Box Protein O3 - genetics; Forkhead Box Protein O3 - metabolism; FOXO3A; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Myocytes, Cardiac - radiation effects; radiation-induced heart disease; Ubiquitination
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.3724/abbs.2024130

Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 ( ) plays an important role in DNA damage repair, but its role in RIHD is less known. In this study, global knockout mice, C57BL/6J mice, and C57BL/6J mice overexpressing are treated with radiation at a total dose of 20 Gy or 0 Gy. After 9 weeks, echocardiography is used to assess cardiac hypertrophy and apoptosis. The results show that deletion exacerbates radiation-induced cardiac hypertrophy and apoptosis, while overexpression has the opposite effect. Further mechanistic investigations reveal that interacts with and destabilizes it by catalyzing its deubiquitination. Inhibition of ameliorates cardiac hypertrophy and apoptosis after knockdown. Thus, protects against radiation-induced cardiac hypertrophy and apoptosis via destabilization of , which may offer new insight into therapeutic strategies for RIHD.