苯并[a]芘和1-羟基芘诱导人胚胎干细胞分化心肌细胞ROS、CYP基因表达和DNA损伤

Benzo[a]pyrene and 1-Hydroxypyrene Induce ROS,CYP Gene Expression and DNA Damage in Human Embryonic Stem Cell Derived Cardiomyocytes

多环芳烃(PAHs)化合物中的苯并[a]芘和PAHs暴露检测标志物1-羟基芘与心脏功能障碍有关,但其生物学机制尚不清楚。为研究苯并[a]芘和1-羟基芘对心脏的毒性作用,基于人胚胎干细胞分化心肌细胞(hESC-CM)研究了苯并[a]芘和1-羟基芘对心肌细胞活性氧(ROS)生成、CYP基因表达和DNA损伤等的影响。结果表明,苯并[a]芘和1-羟基芘对h ESC-CM活性无影响,但能显著增强细胞ROS水平,诱导DNA损伤。此外,苯并[a]芘还能诱导细胞线粒体促凋亡基因的表达。研究表明,苯并[a]芘和1-羟基芘能通过诱导氧化应激和DNA损伤事件导致h ESC-CM损伤,在一定程度上解释了多环芳烃暴露导致心脏疾病的分子机制。

Benzo[a]pyrene,as a carcinogenic polycyclic aromatic hydrocarbon(PAH)compound,has received great concern due to its high health risk.1-hydroxypyrene,a metabolite of pyrene,is widely used as one biomarker for PAHs.Previous studies demonstrated that both benzo[a]pyrene and 1-hydroxypyrene related with cardiac dysfunction,but the biological mechanisms have remained unclear.In the present study,toxic mechanisms of these two PAHs were evaluated using human embryonic stem cell derived cardiomyocytes(hESC-CM).The results showed that both benzo[a]pyrene and 1-hydroxypyrene enhanced the intracellular level of ROS and induced DNA damage.Benzo[a]pyrene also induced an expression of cell mitochondrial proapoptotic gene.Overall,the oxidative stress and DNA damage contributed to PAHs toxicity in cardiomyocytes and probably associated with heart diseases.