Mono-(2-ethylhexyl) phthalate induced ROS-dependent autophagic cell death in human vascular endothelial cells. (October 2017)

• Record Type: Journal Article
• Authors: Liu, Nairong; Jiang, Liping; Sun, Xiance; Yao, Xiaofeng; Zhai, Xingyue; Liu, Xiaofang; Wu, Xueyan; Bai, Yueran; Wang, Shaopeng; Yang, Guang
• Is Part Of: Toxicology in vitro. Volume 44(2017)
• Page Start: 49
• Page End: 56
• Publication Date: 2017-10
• Subjects: Mono-(2-ethylhexyl) phthalate -- Autophagy -- Reactive oxygen species -- Akt1; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2017.06.024
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Mono-(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di-(2-ethylhexyl) phthalate (DEHP). MEHP has toxic effects on cardiovascular system, but the possible molecular mechanisms are not completely elucidated. In our study, 3-methyladenine (3-MA), an autophagosome formation inhibitor, protected the EA.hy926 cells against MEHP cytotoxicity, and rapamycin, an autophagosome formation stimulator, further decreased the cell viability in the MEHP-treated EA.hy926 cells. Thus, autophagy may play an important role in MEHP-induced toxicity. MEHP increased the autophagosome number in EA.hy926 cells detected under transmission electron microscope. Collapses of ΔΨm and reactive oxygen species (ROS) level were increased in a dose-dependent manner under treatment with 0–200 μM MEHP for 24 h. N -acetyl-l -cysteine (NAC), a ROS inhibitor, protected against MEHP-induced cytotoxicity and decreased the protein expression of LC3-II. These findings suggested that MEHP-induced autophagic cell death was ROS-dependent in EA.hy926 cells. Knockdown of Akt1 with Akt1 siRNA aggravated MEHP-induced cell death, and insulin, an Akt1 activator, alleviated MEHP-induced cell death. These results were consistent with the expression of LC3-II using western blot. The phospho-Akt1 (Ser473) (p-Akt1) level was enhanced after pretreatment with NAC. In conclusion, it is possible that ROS elicited autophagy through Akt1 pathway in the MEHP-treated EA.hy926 cells. Highlights: MEHP induced autophagy in EA.hy926 cells. MEHP damaged the EA.hy926 cells through the Akt1 pathway. The autophagy may be associated with oxidative stress.