کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5562515 | 1562701 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mono-(2-ethylhexyl) phthalate induced ROS-dependent autophagic cell death in human vascular endothelial cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
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 ÎΨm 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 44, October 2017, Pages 49-56
Journal: Toxicology in Vitro - Volume 44, October 2017, Pages 49-56
نویسندگان
Nairong Liu, Liping Jiang, Xiance Sun, Xiaofeng Yao, Xingyue Zhai, Xiaofang Liu, Xueyan Wu, Yueran Bai, Shaopeng Wang, Guang Yang,