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Aloe Emodin Alleviates Radiation-Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption.

Author information

Affiliations

  • 1. Department of Cardiovascular Medicine, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, 412000, P. R. China.
      Authors
    • Ouyang F 1
    • Li Y 1
    • Wang H 1
    • Liu X 1
    (4 authors)
  • 2. Zhuzhou Clinical College, Jishou University, Jishou, Hunan, 416000, P. R. China.
      Authors
    • Tan X 2
    • Xie G 2
    • Zhou L 2
    (3 authors)
  • 3. Department of Critical Care Medicine, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, P. R. China.
      Authors
    • Zeng J 3
    (1 author)
  • 4. Clinical Research Institute, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P. R. China.
      Authors
    • Zeng G 4, 9
    • Gao A 4, 7, 9
    (2 authors)
  • 5. Clinical Research Center for Arteriosclerotic Disease in Hunan Province, Hengyang, Hunan, 421001, P. R. China.
      Authors
    • Luo Q 5
    • Chen S 5
    (2 authors)
    • Show all (9)

ORCIDs linked to this article

Advanced Science (Weinheim, Baden-wurttemberg, Germany), 04 Nov 2024, :e2406026
https://doi.org/10.1002/advs.202406026 PMID: 39494721 

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.

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Read article at publisher's site: https://doi.org/10.1002/advs.202406026

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Funding 

Funders who supported this work.

Clinical Research 4310 Program of the First Affiliated Hospital of University of South China (1)

Foundation of Hunan Provincial Key Laboratory (1)

Hengyang Science and Technology Plan Special Fund (1)

Hunan Provincial Postdoctoral Science Foundation (9)

Key Guidance Projects for University of South China (1)

National Natural Science Foundation of China (3)

Research Start-up Fund of the Second Affiliated Hospital of Hengyang Medical College of University of South China (1)

Scientific Research Project of Hunan Provincial Department of Education (1)

Scientific Research Project of Hunan Provincial Health Commission of China (1)

Scientific Research Project of Yun'nan Provincial Department of Education (1)