Gutiérrez-García Ana K, Torres-García Daniel A, De Leon-Rodriguez Antonio
División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, A.C., Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP, 78216, México.
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210, United States.
Toxicol Res (Camb). 2024 Jul 11;13(4):tfae103. doi: 10.1093/toxres/tfae103. eCollection 2024 Aug.
Phthalates are additives used as plasticizers among other uses, classified as endocrine disruptors and may contribute to some metabolic disorders. The aim of this work was to determine the effect of the exposure of diethyl phthalate (DEP) and dibutyl phthalate (DBP) on cell viability and reactive oxygen species (ROS) production, as well as the regulation of sirloins in HepG2 cells.
HepG2 cells were exposed to DEP or DBP at 0.1, 1, 10 and 100 μg/mL, and after 48 or 72 h the gene and protein expression of sirtuins was quantified by qRT-PCR and Western-Blot, respectively.
Results showed that even at a low concentration of 0.1 μg/mL DEP affected the expression of Sirt3 and Sirt4, whereas DBP at 0.1 μg/mL affected Sirt3 and Sirt5 gene expression. Protein analysis showed a reduction in Sirt1 levels at a DEP concentration of 1 μg/mL and higher, while DBP at higher dose (100 μg/mL) decreased Sirt3 protein levels. Cell viability decreased by 20% only at higher dose (100 μg/mL) and ROS production increased at 10 and 100 μg/mL for both phthalates.
These findings indicate that exposure to low concentrations (0.1 μg/mL) of DEP or DBP can negatively influence the expression of some sirtuins.
邻苯二甲酸盐是用作增塑剂等用途的添加剂,被归类为内分泌干扰物,可能导致一些代谢紊乱。本研究的目的是确定邻苯二甲酸二乙酯(DEP)和邻苯二甲酸二丁酯(DBP)暴露对细胞活力和活性氧(ROS)产生的影响,以及对HepG2细胞中沉默调节蛋白的调控。
将HepG2细胞暴露于浓度为0.1、1、10和100μg/mL的DEP或DBP中,48或72小时后,分别通过qRT-PCR和蛋白质免疫印迹法对沉默调节蛋白的基因和蛋白表达进行定量分析。
结果表明,即使在低浓度0.1μg/mL时,DEP也会影响Sirt3和Sirt4的表达,而0.1μg/mL的DBP会影响Sirt3和Sirt5基因的表达。蛋白质分析显示,DEP浓度为1μg/mL及更高时,Sirt1水平降低,而高剂量(100μg/mL)的DBP会降低Sirt3蛋白水平。仅在高剂量(100μg/mL)时细胞活力下降20%,两种邻苯二甲酸盐在10和100μg/mL时ROS产生增加。
这些发现表明,暴露于低浓度(0.1μg/mL)的DEP或DBP会对某些沉默调节蛋白的表达产生负面影响。