Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 Apr 2024
26 Apr 2024
Historique:
received:
06
05
2023
accepted:
16
04
2024
medline:
27
4
2024
pubmed:
27
4
2024
entrez:
26
4
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38670989
doi: 10.1038/s41467-024-47947-5
pii: 10.1038/s41467-024-47947-5
doi:
Substances chimiques
Glutamate-Ammonia Ligase
EC 6.3.1.2
Polyphosphates
0
Adenosine Triphosphate
8L70Q75FXE
Glutamic Acid
3KX376GY7L
Glutamine
0RH81L854J
Manganese
42Z2K6ZL8P
Biocompatible Materials
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3534Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22025701
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22293052
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22177048
Organisme : Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)
ID : BK20220764
Informations de copyright
© 2024. The Author(s).
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