Green Onion-Derived Exosome-like Nanoparticles Prevent Ferroptotic Cell Death Triggered by Glutamate: Implication for GPX4 Expression.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Exosomes*/metabolism ; Exosomes*/drug effects ; Ferroptosis*/drug effects ; Glutamic Acid* ; Phospholipid Hydroperoxide Glutathione Peroxidase*/metabolism ; Nanoparticles* ; Onions*; Animals ; Mice ; Cell Line ; Lipid Peroxidation/drug effects ; Hippocampus/drug effects ; Hippocampus/metabolism ; Iron/metabolism ; Cell Death/drug effects ; Neurons/drug effects ; Neurons/metabolism

In recent years, alongside research on mammalian-derived exosomes, there has been increasing interest in the physiological activities of plant-derived exosome-like nanoparticles (PDEN). The biocompatibility, minimal side effects, and diverse bioactive ingredients contained in PDEN make them valuable as potential therapeutic agents for an extensive range of diseases. In this study, we cost-effectively isolated exosome-like nanoparticles from green onion (Allium fistulosum) using polyethylene glycol and examined their biological activity in HT-22 cells exposed to glutamate. The isolated green onion-derived exosome-like nanoparticle (GDEN) had an average diameter of 167.4 nm and a zeta potential of -16.06 mV. GDEN effectively inhibited glutamate-induced Ca ²⁺ influx and lipid peroxidation, thereby preventing ferroptotic cell death in HT-22 mouse hippocampal cells. Additionally, GDEN reduced the intracellular iron accumulation by modulating the expression of proteins associated with iron metabolism, including transferrin receptor 1, ferroportin 1, divalent metal transporter 1, and ferritin. Notably, GDEN upregulated the expression of glutathione peroxidase 4, a potent antioxidant protein involved in ferroptosis, along with an increase in glutathione synthesis. These findings indicate that GDENs have the potential to serve as bioactives from natural sources against glutamate-induced neuronal cell death, like ferroptosis. This study advances the investigation into the potential medical applications of GDEN and may provide a new approach for the utilization of these bioactive components against neuronal disorders.

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2021R1A2C1007526 A National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)

Keywords: ferroptosis; glutamate; glutathione peroxidase 4; green onion-derived exosome-like nanoparticle; iron accumulation; lipid peroxidation

3KX376GY7L (Glutamic Acid)
EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
EC 1.11.1.9 (glutathione peroxidase 4, mouse)
E1UOL152H7 (Iron)

Date Created: 20241016 Date Completed: 20241016 Latest Revision: 20241019

20241019

PMC11478619

10.3390/nu16193257

39408223