Diethyl phthalate enhances expression of SIRT1 and DNMT3a during apoptosis in PC12 cells
Diethyl phthalate enhances expression of SIRT1 and DNMT3a during apoptosis in PC12 cells
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DOI：
10.1002/jat.2816
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发表时间：
2013-12
影响因子：
3.3
通讯作者：
Yongkun Sun;Zhikun Guo;S. Iku;T. Saito;M. Kurasaki
中科院分区：
文献类型：
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作者：
Yongkun Sun;Zhikun Guo;S. Iku;T. Saito;M. Kurasaki
邻苯二甲酸二乙酯(DEP)是一种邻苯二甲酸酯增塑剂，广泛用于个人护理产品、化妆品、医疗器械和药物涂料中。DEP被认为是一种潜在的内分泌干扰物。先前我们发现DEP促进了血清剥夺诱导的PC12细胞的凋亡。然而，DEP与长寿相关因子、sirtuins和表观遗传因子(如DNA甲基转移酶)的关系尚不清楚，因为化学毒性、sirtuins和表观遗传因子引起的基因组修饰在异常代谢和发育中发挥了关键作用。在这里，我们研究DEP是否影响sirtuins(SIRT1和SIRT2)和甲基转移酶(DNMT1和DNMT3a)对PC12细胞凋亡的影响。我们发现去血清可显著降低DNMT3a的表达。而DNMT3a、DNMT3b和SIRT1在血清剥夺诱导的细胞凋亡过程中显著增加。这些结果表明，SIRT1、DNMT3a和DNMT3b在不同的细胞凋亡阶段中发挥着多种复杂的作用。我们的结果表明，DEP在营养应激条件下触发了表观遗传因子对PC12细胞的凋亡。最后，我们的结果表明，监测DNMT3a、DNMT3b和SIRT1等表观遗传因子可能是进行化学毒性风险评估的有用工具。版权所有©2012 John Wiley&Sons，Ltd.
Diethyl phthalate (DEP) works as a phthalate plasticizer and is ubiquitously used in personal care products, cosmetics, medical equipment and pharmaceutical coating. DEP is considered a potential endocrine disruptor. Previously we found DEP‐enhanced apoptosis induced by serum deprivation in PC12 cells. However, the relationship between DEP and longevity‐related factors, sirtuins and epigenetic factors (e.g. DNA methyltransferases) remains unclear, because genome modification caused by chemical toxicity, sirtuins and epigenetic factors have played key roles in abnormal metabolism and development. Here, we investigate whether DEP affects sirtuins (SIRT1 and SIRT2) and methyltranferases (DNMT1 and DNMT3a) on the apoptosis of PC12 cells. We found that DNMT3a was significantly decreased by serum deprivation. However, DNMT3a, DNMT3b and SIRT1 were significantly increased under the enhancement of apoptosis induced by serum deprivation. These results suggest that SIRT1, DNMT3a and DNMT3b play multiple and complex roles in different apoptotic stages. Our results showed DEP triggered epigenetic factors on PC12 cells apoptosis under nutrition stress. Finally, our results suggest that monitoring epigenetic factors such as DNMT3a, DNMT3b and SIRT1 could be a useful tool for chemical toxicity risk assessment. Copyright © 2012 John Wiley & Sons, Ltd.