Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption
Abstract Aloe emodin is an anthraquinone of traditional Chinese medicine monomer, which plays a protective action in cardiovascular diseases. However, the regulatory mechanisms of aloe emodin in the protection of radiation‐induced heart damage (RIHD) are unclear. As a novel post‐translational modifi...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406026 |
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| author | Fan Ouyang Yaling Li Haoming Wang Xiangyang Liu Xiaoli Tan Genyuan Xie Junfa Zeng Gaofeng Zeng Qiong Luo Hong Zhou Siming Chen Kai Hou Jinren Fang Xia Zhang Linlin Zhou Yukun Li Anbo Gao |
| author_facet | Fan Ouyang Yaling Li Haoming Wang Xiangyang Liu Xiaoli Tan Genyuan Xie Junfa Zeng Gaofeng Zeng Qiong Luo Hong Zhou Siming Chen Kai Hou Jinren Fang Xia Zhang Linlin Zhou Yukun Li Anbo Gao |
| author_sort | Fan Ouyang |
| collection | DOAJ |
| description | Abstract Aloe emodin is an anthraquinone of traditional Chinese medicine monomer, which plays a protective action in cardiovascular diseases. However, the regulatory mechanisms of aloe emodin in the protection of radiation‐induced heart damage (RIHD) are unclear. As a novel post‐translational modification, lactylation is considered as a critical mediator in inflammatory cascade and cardiac injury. Here, using a cross of differential omics and 4D label‐free lactylation omics, protein disulfide‐isomerase (P4HB) is identified as a novel target for lactylation, and aloe emodin inhibits the binding of lactate to the K311 site of P4HB. Aloe emodin stabilizes kynurenine metabolism through inhibition of aspartate aminotransferase (GOT2) accumulation on damaged mitochondria. Mechanistically, aloe emodin inhibits phosphorylated glycogen synthase kinase 3B (p‐GSK3B) transcription in the nucleus to repress the interaction of prostaglandin G/H synthase 2 (PTGS2) with SH3 domain of SH3 domain‐containing GRB2‐like protein B1 (SH3GLB1), thereby disrupting the functions of mitochondrial complexes and reducing SH3GLB1‐mediated mitoROS accumulation, eventually suppressing calcium‐binding and coiled‐coil domain‐containing protein 2 (NDP52)‐induced mitophagy. This study unveils the regulatory role of aloe emodin in RIHD alleviation through PTGS2/SH3GLB1/NDP52 axis, indicates aloe emodin stabilizes GOT2‐mediated kynurenine metabolism through P4HB lactylation. Collectively, this study provides novel insights into the regulatory mechanisms underlying the protective role of aloe emodin in cardiac injury, and opens new avenues for therapeutic strategies of aloe emodin in preventing RIHD by regulating lactylation. |
| format | Article |
| id | doaj-art-9ec71b312a0b479eab3c63e10e47a714 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9ec71b312a0b479eab3c63e10e47a7142025-08-20T02:37:18ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202406026Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic DisruptionFan Ouyang0Yaling Li1Haoming Wang2Xiangyang Liu3Xiaoli Tan4Genyuan Xie5Junfa Zeng6Gaofeng Zeng7Qiong Luo8Hong Zhou9Siming Chen10Kai Hou11Jinren Fang12Xia Zhang13Linlin Zhou14Yukun Li15Anbo Gao16Department of Cardiovascular Medicine Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University Zhuzhou Hunan 412000 P. R. ChinaDepartment of Cardiovascular Medicine Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University Zhuzhou Hunan 412000 P. R. ChinaDepartment of Cardiovascular Medicine Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University Zhuzhou Hunan 412000 P. R. ChinaDepartment of Cardiovascular Medicine Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University Zhuzhou Hunan 412000 P. R. ChinaZhuzhou Clinical College Jishou University Jishou Hunan 416000 P. R. ChinaZhuzhou Clinical College Jishou University Jishou Hunan 416000 P. R. ChinaDepartment of Critical Care Medicine Hengyang Medical School The Second Affiliated Hospital University of South China Hengyang Hunan 421001 P. R. ChinaClinical Research Institute The Second Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaClinical Research Center for Arteriosclerotic Disease in Hunan Province Hengyang Hunan 421001 P. R. ChinaDepartment of Radiology Hengyang Medical School The First Affiliated Hospital University of South China Hengyang Hunan 421001 P. R. ChinaClinical Research Center for Arteriosclerotic Disease in Hunan Province Hengyang Hunan 421001 P. R. ChinaDepartment of Cardiovascular Medicine The Second Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Cardiovascular Medicine The Second Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaDepartment of Ultrasound Medicine Hengyang Medical School The Second Affiliated Hospital University of South China Hengyang Hunan 421001 P. R. ChinaZhuzhou Clinical College Jishou University Jishou Hunan 416000 P. R. ChinaDepartment of Cardiovascular Medicine The Second Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaClinical Research Institute The Second Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 P. R. ChinaAbstract Aloe emodin is an anthraquinone of traditional Chinese medicine monomer, which plays a protective action in cardiovascular diseases. However, the regulatory mechanisms of aloe emodin in the protection of radiation‐induced heart damage (RIHD) are unclear. As a novel post‐translational modification, lactylation is considered as a critical mediator in inflammatory cascade and cardiac injury. Here, using a cross of differential omics and 4D label‐free lactylation omics, protein disulfide‐isomerase (P4HB) is identified as a novel target for lactylation, and aloe emodin inhibits the binding of lactate to the K311 site of P4HB. Aloe emodin stabilizes kynurenine metabolism through inhibition of aspartate aminotransferase (GOT2) accumulation on damaged mitochondria. Mechanistically, aloe emodin inhibits phosphorylated glycogen synthase kinase 3B (p‐GSK3B) transcription in the nucleus to repress the interaction of prostaglandin G/H synthase 2 (PTGS2) with SH3 domain of SH3 domain‐containing GRB2‐like protein B1 (SH3GLB1), thereby disrupting the functions of mitochondrial complexes and reducing SH3GLB1‐mediated mitoROS accumulation, eventually suppressing calcium‐binding and coiled‐coil domain‐containing protein 2 (NDP52)‐induced mitophagy. This study unveils the regulatory role of aloe emodin in RIHD alleviation through PTGS2/SH3GLB1/NDP52 axis, indicates aloe emodin stabilizes GOT2‐mediated kynurenine metabolism through P4HB lactylation. Collectively, this study provides novel insights into the regulatory mechanisms underlying the protective role of aloe emodin in cardiac injury, and opens new avenues for therapeutic strategies of aloe emodin in preventing RIHD by regulating lactylation.https://doi.org/10.1002/advs.202406026aloe emodinkynurenine metabolismlactylationmitophagyradiation‐induced heart damage |
| spellingShingle | Fan Ouyang Yaling Li Haoming Wang Xiangyang Liu Xiaoli Tan Genyuan Xie Junfa Zeng Gaofeng Zeng Qiong Luo Hong Zhou Siming Chen Kai Hou Jinren Fang Xia Zhang Linlin Zhou Yukun Li Anbo Gao Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption Advanced Science aloe emodin kynurenine metabolism lactylation mitophagy radiation‐induced heart damage |
| title | Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption |
| title_full | Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption |
| title_fullStr | Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption |
| title_full_unstemmed | Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption |
| title_short | Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption |
| title_sort | aloe emodin alleviates radiation induced heart disease via blocking p4hb lactylation and mitigating kynurenine metabolic disruption |
| topic | aloe emodin kynurenine metabolism lactylation mitophagy radiation‐induced heart damage |
| url | https://doi.org/10.1002/advs.202406026 |
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