The role of ANXA5 in DBP-induced oxidative stress through ERK/Nrf2 pathway

Publication date: Available online 1 August 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Lei Zhang, Zhiqiang Qin, Ran Li, Shangqian Wang, Wei Wang, Min Tang, Wei ZhangAbstractDi-N-butylphthalate (DBP) have given rise to more and more attention due to its unique endocrine toxicity to male reproductive system. Our previous studies have demonstrated antioxidative Nrf2 (nuclear factor erythroid related factor 2) pathway play a vital role in DBP induced oxidative stress injury. ANXA5 (annexin A5), which is highly expressed in testicular Leydig and Sertoli cells, was found upregulated after DBP stimulation. Mouse Leydig and Sertoli cells were exposed to different concentration of DBP for 24 hours to examine the ROS (Reactive oxygen species), MDA (Malondialdehyde), SOD (superoxide dismutase) level and ANXA5, Nrf2, NQO1 (NAD(P)H-quinone oxidoreductase 1), HO-1 (heme oxygenase 1) and ERK/P-ERK protein expression by DHE (Dihydroethidium) staining, ELISA (enzyme-linked immunosorbent assay) and Western blot respectively. Firstly, the oxidative stress injury induced by DBP was re-validated. Then, we confirmed the change of Nrf2 pathway and ANXA5 level after DBP exposure to testicular cells. Additionally, overexpressed ANXA5 could activate Nrf2/HO-1/NQO1 antioxidant pathway and significantly attenuate DBP-induced oxidative stress. Ultimately, we demonstrated ANXA5 could increase ERK phosphorylated level and the activated role of ANXA5 on ERK/Nrf2 pathway could be rever...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research