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Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells

Author

Listed:
  • Jing Wang

    (Nanjing University)

  • Xinyang Zhao

    (Nanjing University)

  • Yucheng Tao

    (Nanjing University)

  • Xiuxiu Wang

    (Nanjing University)

  • Li Yan

    (Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area)

  • Kuang Yu

    (Tsinghua University)

  • Yi Hsu

    (Taipei Wego Private Senior High School)

  • Yuncong Chen

    (Nanjing University
    Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area)

  • Jing Zhao

    (Nanjing University
    Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area
    Nanjing University)

  • Yong Huang

    (The Hong Kong University of Science and Technology)

  • Wei Wei

    (Nanjing University
    Nanjing University
    Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area
    Nanjing University)

Abstract

Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.

Suggested Citation

  • Jing Wang & Xinyang Zhao & Yucheng Tao & Xiuxiu Wang & Li Yan & Kuang Yu & Yi Hsu & Yuncong Chen & Jing Zhao & Yong Huang & Wei Wei, 2024. "Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47947-5
    DOI: 10.1038/s41467-024-47947-5
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    References listed on IDEAS

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    1. Chi Yao & Yuwei Xu & Jianpu Tang & Pin Hu & Hedong Qi & Dayong Yang, 2022. "Dynamic assembly of DNA-ceria nanocomplex in living cells generates artificial peroxisome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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