Effects of oxidative stress-induced increases in Zn2+ concentrations in human gingival epithelial cells.

Hiroko Yagi, Chiharu Fujihara, Shinya Murakami

Journal of periodontal research 2021 Jun

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Previous studies have reported that oxidative stress increases intracellular Zn2+ concentrations and induces cytotoxicity. However, no studies have investigated whether oxidative stress induces such changes in periodontal tissue cells. In the present study, we investigated the effect of oxidative stress on intracellular Zn2+ concentration in periodontium constituent cells and its potential relationship with periodontal disease. We analyzed changes in intracellular Zn2+ concentrations in human gingival epithelial (epi4) cells treated with hydrogen peroxide (H2 O2 ). The fluorescent probes FluoZin-3 AM and CellTracker Green CMFDA were used to detect intracellular Zn2+ and thiol groups, respectively. Western blot analyses, luciferase reporter assays, and real-time polymerase chain reaction (PCR) analyses were performed to examine the effect of intracellular Zn2+ on epi4 cells. H2 O2 treatment increased intracellular concentrations of Zn2+ in epi4 cells by facilitating the movement of Zn2+ from cellular nonprotein thiols to the cytoplasm and promoting cell membrane permeability to Zn2+ . Furthermore, H2 O2 -induced increases in intracellular Zn2+ activated the p38 cAMP response element-binding protein/mitogen-activated protein kinase (p38 CREB/MAPK) cascade, upregulated nuclear factor kappa B (NF-κB) DNA binding, and increased the expression of inflammatory cytokines and matrix metallopeptidase-9 (MMP-9). Increases in intracellular Zn2+ induced by oxidative stress activate signaling pathways involved in inflammation, potentially contributing to the progression of periodontal disease. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Hiroko Yagi, Chiharu Fujihara, Shinya Murakami. Effects of oxidative stress-induced increases in Zn2+ concentrations in human gingival epithelial cells. Journal of periodontal research. 2021 Jun;56(3):512-522