Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy
| العنوان: | Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy |
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| المؤلفون: | Jian Kang, Jun Cao, Xiaofeng Yao, Yuexia Wang, Yufang Ma, Xiance Sun, Min Chen, Shanshan Sha, Liping Jiang |
| المصدر: | Toxicological Sciences. 153:198-211 |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Autophagosome, Fluorocarbons, Gene knockdown, Chemistry, ATG5, Autophagy, Mitophagy, Cathepsin D, Apoptosis, PINK1, Hep G2 Cells, Toxicology, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Alkanesulfonic Acids, 030220 oncology & carcinogenesis, Humans, RNA Interference |
| الوصف: | Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a specific molecule that linked autophagy with LMP. PFOS-induced collapse of mitochondrial transmembrane potential was cathepsin D and autophagy dependent. Addition of 3-MA relieved PFOS-induced apoptosis, which was evidenced by Hoechst assay, AV/PI staining and caspase-3 activity assay. Inhibition of autophagosome formation by Atg5 siRNA attenuated PFOS-induced apoptosis. Treatment of HepG2 cells with PFOS for 24 h impaired mitophagy, as evidenced by an increase of cells with giant mitochondria and impairment of colocalization of PINK1 with light chain 3. In summary, we report that PFOS induces autophagy-dependent apoptosis in HepG2 cells through the lysosomal-mitochondrial axis and impairment of mitophagy, suggesting that autophagy is a primary target for PFOS toxicity. These findings provide new mechanistic insights into PFOS-induced hepatotoxicity. |
| تدمد: | 1096-0929 1096-6080 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ab302c73b8b608ef72a0153ff8270eTest https://doi.org/10.1093/toxsci/kfw118Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e8ab302c73b8b608ef72a0153ff8270e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10960929 10966080 |
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