Zn0-Induced Cytotoxicity and Mitochondrial Stress in Microglia: Implications of the Protective Role of Immunoglobulin G In Vitro

Autor: Katarina Živančević, Başak Aru, Abdullah Demir, Lidija Radenović, Pavle Andjus, Gülderen Yanıkkaya Demirel
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Balkan Medical Journal, Vol 41, Iss 5, Pp 348-356 (2024)
Druh dokumentu: article
ISSN: 2146-3123
2146-3131
DOI: 10.4274/balkanmedj.galenos.2024.2024-4-119
Popis: Background: Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders. Aims: To investigate whether IgG treatment can alleviate oxidative stress caused by Zn0 on microglia in vitro. Study Design: In vitro study. Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn0 cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn0 neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn0-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn0-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn0 exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn0 decreased TRIM21 levels, which is reversed by IgG administration. Conclusion: These findings elucidate the cellular responses to Zn0 and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn0 exposure.
Databáze: Directory of Open Access Journals
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