Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress
A sudden increase in ambient oxygen concentration after birth forces the metabolic switch from anaerobic glycolysis to oxidative phosphorylation, which contributes to the rapid decline of cardiomyocyte proliferation. Lactate dehydrogenase A (LDHA), a metabolic enzyme normally localized in the cytopl...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Journal of Cardiovascular Development and Disease |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2308-3425/12/7/278 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849406517348925440 |
|---|---|
| author | Mengfei Cao Jie Luo Kewei Fu Yao Xu Yinyu Wang Junying Duan Rui Chen Wei Yuan |
| author_facet | Mengfei Cao Jie Luo Kewei Fu Yao Xu Yinyu Wang Junying Duan Rui Chen Wei Yuan |
| author_sort | Mengfei Cao |
| collection | DOAJ |
| description | A sudden increase in ambient oxygen concentration after birth forces the metabolic switch from anaerobic glycolysis to oxidative phosphorylation, which contributes to the rapid decline of cardiomyocyte proliferation. Lactate dehydrogenase A (LDHA), a metabolic enzyme normally localized in the cytoplasm, has been reported to regulate cardiomyocyte proliferation via inducing metabolic reprogramming. Nuclear LDHA has been observed in multiple proliferative cells, whereas the role of LDHA nuclear translocation in cardiomyocyte proliferation remains unresolved. Here we found that the expression of nuclear LDHA was induced both in the infarct area of myocardial infarction (MI) in mice and hypoxic cardiomyocytes in vitro. Mechanically, mild hypoxia prompted metabolic reprogramming which motivated cardiomyocyte proliferation by alleviating reactive oxygen species (ROS), while severe hypoxia coincided with oxidative stress that induced cardiomyocyte cell cycle arrest. Interestingly, LDHA nuclear translocation in cardiomyocytes occurred in response to oxidative stress, and blocking of nuclear LDHA resulted in elevated ROS generation. Collectively, our findings uncover a non-canonical role of nuclear LDHA in maintaining redox balance and resisting cardiomyocyte cell cycle arrest. |
| format | Article |
| id | doaj-art-a05e290e24ef47d3a8bc09994727f1fd |
| institution | Kabale University |
| issn | 2308-3425 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj-art-a05e290e24ef47d3a8bc09994727f1fd2025-08-20T03:36:21ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252025-07-0112727810.3390/jcdd12070278Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative StressMengfei Cao0Jie Luo1Kewei Fu2Yao Xu3Yinyu Wang4Junying Duan5Rui Chen6Wei Yuan7Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Yixing People’s Hospital, Yixing 214200, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, ChinaA sudden increase in ambient oxygen concentration after birth forces the metabolic switch from anaerobic glycolysis to oxidative phosphorylation, which contributes to the rapid decline of cardiomyocyte proliferation. Lactate dehydrogenase A (LDHA), a metabolic enzyme normally localized in the cytoplasm, has been reported to regulate cardiomyocyte proliferation via inducing metabolic reprogramming. Nuclear LDHA has been observed in multiple proliferative cells, whereas the role of LDHA nuclear translocation in cardiomyocyte proliferation remains unresolved. Here we found that the expression of nuclear LDHA was induced both in the infarct area of myocardial infarction (MI) in mice and hypoxic cardiomyocytes in vitro. Mechanically, mild hypoxia prompted metabolic reprogramming which motivated cardiomyocyte proliferation by alleviating reactive oxygen species (ROS), while severe hypoxia coincided with oxidative stress that induced cardiomyocyte cell cycle arrest. Interestingly, LDHA nuclear translocation in cardiomyocytes occurred in response to oxidative stress, and blocking of nuclear LDHA resulted in elevated ROS generation. Collectively, our findings uncover a non-canonical role of nuclear LDHA in maintaining redox balance and resisting cardiomyocyte cell cycle arrest.https://www.mdpi.com/2308-3425/12/7/278nuclear lactate dehydrogenase Acardiomyocyte proliferationoxidative stresshypoxia |
| spellingShingle | Mengfei Cao Jie Luo Kewei Fu Yao Xu Yinyu Wang Junying Duan Rui Chen Wei Yuan Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress Journal of Cardiovascular Development and Disease nuclear lactate dehydrogenase A cardiomyocyte proliferation oxidative stress hypoxia |
| title | Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress |
| title_full | Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress |
| title_fullStr | Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress |
| title_full_unstemmed | Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress |
| title_short | Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress |
| title_sort | nuclear lactate dehydrogenase a resists cardiomyocyte cell cycle arrest induced by oxidative stress |
| topic | nuclear lactate dehydrogenase A cardiomyocyte proliferation oxidative stress hypoxia |
| url | https://www.mdpi.com/2308-3425/12/7/278 |
| work_keys_str_mv | AT mengfeicao nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT jieluo nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT keweifu nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT yaoxu nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT yinyuwang nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT junyingduan nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT ruichen nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress AT weiyuan nuclearlactatedehydrogenasearesistscardiomyocytecellcyclearrestinducedbyoxidativestress |