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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
引用本文:吴彬彬,晏斌,胡梅,陈曦,梁岩.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[J].生态毒理学报,2020,15(2):96-103.
作者姓名:吴彬彬  晏斌  胡梅  陈曦  梁岩
作者单位:1. 中国科学院深圳先进技术研究院,深圳 518055 2. 中国科学院大学,北京 100049 3. 香港大学李嘉诚医学院,香港 4. 山东省食品药品检验研究院,济南 250101 5. 电子科技大学资源与环境学院,成都 611731
基金项目:广东省科技计划项目(2016A020214015);电子科技大学科研启动基金资助项目(Y03019023601008022);中国科学院战略性先导科技专项(XDA20060303)
摘    要: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。

关 键 词:多环芳烃  胚胎干细胞分化心肌细胞  DNA损伤
收稿时间:2019/5/27 0:00:00
修稿时间:2019/7/24 0:00:00

Benzo[a]pyrene and 1-Hydroxypyrene Induce ROS, CYP Gene Expression and DNA Damage in Human Embryonic Stem Cell Derived Cardiomyocytes
Wu Binbin,Yan Bin,Hu Mei,Chen Xi,Liang Yan.Benzo[a]pyrene and 1-Hydroxypyrene Induce ROS, CYP Gene Expression and DNA Damage in Human Embryonic Stem Cell Derived Cardiomyocytes[J].Asian Journal of Ecotoxicology,2020,15(2):96-103.
Authors:Wu Binbin  Yan Bin  Hu Mei  Chen Xi  Liang Yan
Institution:1. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 2. University of Chinese Academy of Sciences, Beijing 100049, China 3. LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China 4. Shandong Institute for Food and Drug Control, Ji''nan 250101, China 5. School of Resources and Environment, University of Electronic Science and Technology of China, Chengdu 611731, China
Abstract:Benzoa]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 benzoa]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 benzoa]pyrene and 1-hydroxypyrene enhanced the intracellular level of ROS and induced DNA damage. Benzoa]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.
Keywords:polycyclic aromatic hydrocarbon  human embryonic stem cells derived cardiomyocytes  DNA damage
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