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

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 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.

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.