کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5560129 | 1403309 | 2017 | 10 صفحه PDF | دانلود رایگان |

- 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 926Â cells with MEHP induced autophagy at earlier time (6Â h) in this study. Lysosomal membrane permeabilization (LMP) occurred, after treatment with MEHP for 12Â 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 926Â 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 926Â cells through the lysosomal-mitochondrial axis. This study provides new mechanistic insights into MEHP-induced cardiovascular toxicity.
Journal: Food and Chemical Toxicology - Volume 106, Part A, August 2017, Pages 273-282