Shen B, Wang W, Ding L, Sao Y, Huang Y, Shen Z, Zhuo Y, Wei Z, Zhang W
Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Hum Exp Toxicol. 2015 Feb;34(2):145-52. doi: 10.1177/0960327114530744. Epub 2014 Jun 10.
This study aimed to determine whether nuclear factor erythroid 2-related factor 2 antagonized the oxidative stress induced by di-N-butylphthalate (DBP) in testicular Leydig cells.
Mouse TM3 testicular Leydig cells were treated with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP. Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and the effects of Nrf2 inducer sulphoraphane (SFN) were tested.
DBP induced intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and protein levels of Nrf2 were increased together with its target genes, namely heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP.
Increased Nrf2 activity, for example, by SFN can effectively antagonize the oxidative stress in testicular Leydig cells caused by DBP.
本研究旨在确定核因子红细胞2相关因子2是否能拮抗邻苯二甲酸二丁酯(DBP)诱导的睾丸间质细胞氧化应激。
在有和没有DBP的情况下,对小鼠TM3睾丸间质细胞进行Nrf2基因敲低(KD)或过表达处理。检测氧化状态。研究Nrf2靶抗氧化基因,并测试Nrf2诱导剂萝卜硫素(SFN)的作用。
DBP诱导的细胞内氧化应激程度与Nrf2基因敲低相似。DBP刺激后,Nrf2及其靶基因(即血红素加氧酶1、烟酰胺腺嘌呤二核苷酸磷酸醌氧化还原酶1和过氧化物酶体增殖物激活受体6)的表达和蛋白水平均升高。使用SFN不仅能恢复细胞内氧化毒性,还能恢复细胞增殖以及DBP刺激后的睾酮分泌。
例如,通过SFN提高Nrf2活性可有效拮抗DBP引起的睾丸间质细胞氧化应激。