کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5560129 1403309 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mono(2-ethylhexyl) phthalate induces autophagy-dependent apoptosis through lysosomal-mitochondrial axis in human endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش تغذیه
پیش نمایش صفحه اول مقاله
Mono(2-ethylhexyl) phthalate induces autophagy-dependent apoptosis through lysosomal-mitochondrial axis in human endothelial cells
چکیده انگلیسی


- MEHP-induced apoptosis was autophagy-dependent.
- Lysosomal-mitochondrial axis was the main pathway.
- Autophagy triggered LMP, MOMP and apoptosis induced by MEHP.

Mono(2-ethylhexyl) phthalate (MEHP), the active metabolite of di(2-ethylhexyl) phthalate (DEHP), has been known to have adverse effects on the reproductive system, urologic systems, hepatic, developmental toxicities and carcinogenicity. However, the effect of MEHP on cardiovascular toxicity remains unclear. Therefore, we aimed to evaluate the cytotoxic effects of MEHP and the possible molecular mechanism. We found that treatment of EA.hy 926 cells with MEHP induced autophagy at earlier time (6 h) in this study. Lysosomal membrane permeabilization (LMP) occurred, after treatment with MEHP for 12 h, followed by the release of cathepsin B. Autophagy inhibitor 3-methyladenine (3MA) attenuated MEHP-induced LMP and the release of cathepsin B in EA.hy 926 cells. Additionally, MEHP induced collapse of mitochondrial transmembrane potential, which was evidenced by JC-1 staining. Addition of 3MA relieved MEHP-induced apoptosis as assessed by the expression of caspase 3 and TUNEL assay, indicating that MEHP-induced apoptosis was autophagy-dependent. Cathepsin B inhibitor, CA-074 Me, suppressed MEHP-induced the mitochondria release of cytochrome c and apoptosis as well. In summary, our results suggest that MEHP induced autophagy-dependent apoptosis in EA.hy 926 cells through the lysosomal-mitochondrial axis. This study provides new mechanistic insights into MEHP-induced cardiovascular toxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 106, Part A, August 2017, Pages 273-282
نویسندگان
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