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

Overview

Journal Balkan Med J

Publisher Galenos Publishing House

Specialty General Medicine

Date 2024 Aug 12

PMID 39129512

Authors

Katarina Zivancevic

Basak Aru

Abdullah Demir

Lidija Radenovic

Pavle Andjus

Gulderen Yanikkaya Demirel

Affiliations

Soon will be listed here.

Abstract

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 Zn on microglia in vitro.

Study Design: In vitro study.

Methods: The feasibility of Zn treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn, 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 Zn cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn 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 Zn-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn decreased TRIM21 levels, which is reversed by IgG administration.

Conclusion: These findings elucidate the cellular responses to Zn and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn exposure.

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