HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice
Abstract Histone deacetylase enzymes (HDACs) regulate protein acetylation. HDAC1 is known to enhance ischemia/reperfusion (I/R) injury, but its underlying mechanism(s) of action have not been defined. Here, in vivo mouse models of myocardial I/R were used to investigate the role of HDAC1 during I/R...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01308-1 |
| _version_ | 1797946054854836224 |
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| author | Zhenhua Wu Yunpeng Bai Yujuan Qi Chao Chang Yan Jiao Yaobang Bai Zhigang Guo |
| author_facet | Zhenhua Wu Yunpeng Bai Yujuan Qi Chao Chang Yan Jiao Yaobang Bai Zhigang Guo |
| author_sort | Zhenhua Wu |
| collection | DOAJ |
| description | Abstract Histone deacetylase enzymes (HDACs) regulate protein acetylation. HDAC1 is known to enhance ischemia/reperfusion (I/R) injury, but its underlying mechanism(s) of action have not been defined. Here, in vivo mouse models of myocardial I/R were used to investigate the role of HDAC1 during I/R myocardial injury. We show that HDAC1 enhances the inflammatory responses of I/R mice. Using a constructed macrophage H/R (hypoxia/ regeneration) injury model (Raw264.7 cells), we identified Nur77 as a HDAC1 target in macrophages. Nur77 deficient macrophages failed to downregulate IDH1 (isocitrate dehydrogenase 1) and accumulated succinic acid and other tricarboxylic acid (TCA) cycle-derived metabolites in a glutamine-independent manner. These data show that the inhibition of HDAC1 ameliorates H/R-inflammation in macrophages through the regulation of Nur77 and the TCA cycle. |
| first_indexed | 2024-04-10T21:05:57Z |
| format | Article |
| id | doaj.art-ec78871ff685484b993f88c3b6db4e02 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-10T21:05:57Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-ec78871ff685484b993f88c3b6db4e022023-01-22T12:04:58ZengNature Publishing GroupCell Death Discovery2058-77162023-01-01911910.1038/s41420-023-01308-1HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion miceZhenhua Wu0Yunpeng Bai1Yujuan Qi2Chao Chang3Yan Jiao4Yaobang Bai5Zhigang Guo6Academy of Medical Engineering and Translational Medicine, Tianjin UniversityDepartment of Cardiac Surgery, Tianjin Chest HospitalICU, Department of Cardiac Surgery, Tianjin Chest HospitalICU, Department of Cardiac Surgery, Tianjin Chest HospitalICU, Department of Cardiac Surgery, Tianjin Chest HospitalICU, Department of Cardiac Surgery, Tianjin Chest HospitalAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityAbstract Histone deacetylase enzymes (HDACs) regulate protein acetylation. HDAC1 is known to enhance ischemia/reperfusion (I/R) injury, but its underlying mechanism(s) of action have not been defined. Here, in vivo mouse models of myocardial I/R were used to investigate the role of HDAC1 during I/R myocardial injury. We show that HDAC1 enhances the inflammatory responses of I/R mice. Using a constructed macrophage H/R (hypoxia/ regeneration) injury model (Raw264.7 cells), we identified Nur77 as a HDAC1 target in macrophages. Nur77 deficient macrophages failed to downregulate IDH1 (isocitrate dehydrogenase 1) and accumulated succinic acid and other tricarboxylic acid (TCA) cycle-derived metabolites in a glutamine-independent manner. These data show that the inhibition of HDAC1 ameliorates H/R-inflammation in macrophages through the regulation of Nur77 and the TCA cycle.https://doi.org/10.1038/s41420-023-01308-1 |
| spellingShingle | Zhenhua Wu Yunpeng Bai Yujuan Qi Chao Chang Yan Jiao Yaobang Bai Zhigang Guo HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice Cell Death Discovery |
| title | HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice |
| title_full | HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice |
| title_fullStr | HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice |
| title_full_unstemmed | HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice |
| title_short | HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice |
| title_sort | hdac1 disrupts the tricarboxylic acid tca cycle through the deacetylation of nur77 and promotes inflammation in ischemia reperfusion mice |
| url | https://doi.org/10.1038/s41420-023-01308-1 |
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