Spagnuolo G, Galler K, Schmalz G, Cosentino C, Rengo S, Schweikl H
Department of Oral and Maxillo-Facial Sciences, University of Naples Federico II, Italy.
J Dent Res. 2004 Sep;83(9):703-7. doi: 10.1177/154405910408300909.
Cytotoxicity of triethylene glycol dimethacrylate (TEGDMA), a co-monomer of dental resinous restorative materials, is firmly established in vitro, but the molecular mechanisms are unknown. Here we examined apoptosis and necrosis induced by TEGDMA in human primary pulp cells. The levels of apoptotic and necrotic cell populations differentially increased after exposure to increasing concentrations of TEGDMA. A two-fold increase in the percentage of apoptotic cells was induced by 1 mmol/L TEGDMA. However, a population shift among cells in apoptosis and necrosis was detected when cell cultures were exposed to 2 mmol/L TEGDMA. Inhibition of the MAP Kinase/ERK pathway had no influence on cell survival, but inhibition of phosphatidylinositol 3 kinase (PI3-Kinase; Akt/protein kinase B) by LY294002 amplified TEGDMA-induced apoptosis. Moreover, Akt phosphorylation was inhibited in the presence of TEGDMA. These results suggest that depression of PI3K signaling may be a primary target in TEGDMA-induced apoptosis.
牙科树脂修复材料的共聚单体二甲基丙烯酸三乙二醇酯（TEGDMA）的细胞毒性在体外已得到确证，但其分子机制尚不清楚。在此，我们研究了TEGDMA诱导人原代牙髓细胞凋亡和坏死的情况。暴露于浓度不断增加的TEGDMA后，凋亡和坏死细胞群体的水平呈不同程度增加。1 mmol/L TEGDMA诱导凋亡细胞百分比增加两倍。然而，当细胞培养物暴露于2 mmol/L TEGDMA时，检测到凋亡和坏死细胞群体发生了变化。抑制丝裂原活化蛋白激酶/细胞外信号调节激酶（MAP Kinase/ERK）通路对细胞存活没有影响，但LY294002抑制磷脂酰肌醇3激酶（PI3 - Kinase；Akt/蛋白激酶B）会放大TEGDMA诱导的凋亡。此外，在存在TEGDMA的情况下，Akt磷酸化受到抑制。这些结果表明，PI3K信号传导的抑制可能是TEGDMA诱导凋亡的主要靶点。
