Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA

Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA
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DOI:
10.1016/j.biomaterials.2004.03.021
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发表时间:
2005-03-01
期刊:
影响因子:
14
通讯作者:
Jeng, JH
Jeng, JH
中科院分区:
工程技术1区
文献类型:
--
作者:
Chang, HH;Guo, MK;Jeng, JH

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甲基丙烯酸2-羟乙酯(HEMA)是树脂改性玻璃离子水门汀和牙科粘接剂中释放的主要成分。受HEMA影响的人体组织主要是口腔上皮和牙髓。我们用不同浓度的HEMA处理人牙龈上皮S-G细胞和牙髓成纤维细胞(HPF),以评估其对细胞生长、细胞周期进程、细胞内谷胱甘肽(GSH)水平和活性氧(ROS)产生的影响。HEMA以剂量依赖性方式诱导HPF和S-G细胞的生长抑制,这可能部分地通过诱导细胞周期扰动来解释。在HPF暴露于5和10 mM的HEMA后,观察到G(2)/M期阻滞,同时伴有谷胱甘肽耗竭和ROS产生。当用2.5和5 mm处理时,S-G细胞发生S期阻滞,而在10 mm处观察到亚G(0)/G(1)峰,表明可能诱导凋亡。仅在5和10 mM浓度下,S-G细胞中的GSH耗竭显著,但在1 mM浓度下观察到过量的ROS产生,并在1和5 mm之间随剂量增加而增加,然后在10 mm时减少。这表明S-G细胞中ROS的增加主要不是由GSH耗竭引起的。这些结果有助于确定HEMA引起细胞毒性的机制。(C)2004爱思唯尔有限公司保留所有权利。
2-Hydroxy-ethyl methacrylate (HEMA) is the major component released from resin-modified glass ionomer cements and dental adhesives. Human tissues mainly affected by HEMA are oral epithelium and dental pulp. We treated human gingival epithelial S-G cells and pulp fibroblasts (HPF) with various concentrations of HEMA, to evaluate its effects on cell growth, cell cycle progression, intracellular glutathione (GSH) level and reactive oxygen species (ROS) production. HEMA-induced growth inhibition in HPF and S-G cells in a dose-dependent manner, which may be partially explained by induction of cell cycle perturbation. G(2)/M phase arrest was noted after exposure of HPF to 5 and 10 mM of HEMA, concomitant with glutathione depletion and ROS production. S-phase arrest occurred in S-G cells when treated with 2.5 and 5 mm, while at 10 mm a sub-G(0)/G(1) peak was noted, indicating the potential induction of apoptosis. GSH depletion was marked in S-G cells only at concentrations of 5 and 10 mM, but excessive ROS production was noted at concentration of 1 mM and rose with dose increase between 1 and 5 mm, then lessened at 10 mm. This suggested that the increase of ROS in S-G cells was not mainly caused by GSH depletion. These results helped to define the mechanism of the cytotoxicity caused by HEMA. (C) 2004 Elsevier Ltd. All rights reserved.