Effects of oxidative stress-induced increases in Zn 2+ concentrations in human gingival epithelial cells
Effects of oxidative stress-induced increases in Zn 2+ concentrations in human gingival epithelial cells
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氧化应激引起的人牙龈上皮细胞中Zn 2 浓度增加的影响
DOI：
10.1111/jre.12851
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发表时间：
2021
影响因子：
3.5
通讯作者：
Murakami Shinya
中科院分区：
文献类型：
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作者：
Yagi Hiroko;Fujihara Chiharu;Murakami Shinya
背景与目的以往的研究表明，氧化应激可增加细胞内锌离子浓度，诱导细胞毒性。然而，没有研究调查是否氧化应激诱导牙周组织细胞的这种变化。在本研究中，我们探讨了氧化应激对牙周组织组成细胞内锌离子浓度的影响及其与牙周病的潜在关系。MethodsWe分析了用过氧化氢（H2 O2）处理的人牙龈上皮（epi 4）细胞内锌离子浓度的变化。荧光探针FluoZin-3 AM和CellTracker绿色CMFDA分别用于检测细胞内Zn 2+和巯基。结果H2 O2处理epi 4细胞后，细胞内Zn 2+浓度明显升高，其机制可能是通过促进Zn 2+从非蛋白质巯基向细胞质的迁移和促进细胞膜对Zn 2+的通透性来实现的。此外，H2 O2诱导的细胞内Zn 2+增加激活了p38 cAMP反应元件结合蛋白/丝裂原活化蛋白激酶（p38 CREB/MAPK）级联反应，上调核因子κ B（NF-κB B）DNA结合，并增加炎症细胞因子和基质金属肽酶-9（MMP-9）的表达。结论氧化应激诱导的细胞内Zn 2+增加激活参与炎症的信号通路，可能导致牙周病的发展。
Background and objectivePrevious 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.MethodsWe analyzed changes in intracellular Zn2+concentrations in human gingival epithelial (epi4) cells treated with hydrogen peroxide (H2O2). 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.ResultsH2O2treatment 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, H2O2‐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).ConclusionIncreases in intracellular Zn2+induced by oxidative stress activate signaling pathways involved in inflammation, potentially contributing to the progression of periodontal disease.