Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
| العنوان: | Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells |
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| المؤلفون: | Guang Yang, Qiujuan Li, Xiaofeng Yao, Liping Jiang, Xiaofang Liu, Chengyan Geng, Yuexia Wang, Min Chen, Ya-Nan Liu, Xiance Sun |
| المصدر: | Toxins Volume 7 Issue 8 Pages 3030-3044 Toxins, Vol 7, Iss 8, Pp 3030-3044 (2015) |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Autophagosome, autophagy, Health, Toxicology and Mutagenesis, ATG5, lcsh:Medicine, Cathepsin D, Caspase 3, Biology, Toxicology, Permeability, Article, chemistry.chemical_compound, Humans, lysosomal membrane permeabilization, human liver HepG2 cells, Membrane potential, Membrane Potential, Mitochondrial, lcsh:R, Autophagy, apoptosis, Aurovertins, Hep G2 Cells, Intracellular Membranes, citreoviridin, Mycotoxins, Cell biology, chemistry, Apoptosis, Lysosomes, Pepstatin |
| الوصف: | Citreoviridin (CIT) is a mycotoxin derived from fungal species in moldy cereals. In our previous study, we reported that CIT stimulated autophagosome formation in human liver HepG2 cells. Here, we aimed to explore the relationship of autophagy with lysosomal membrane permeabilization and apoptosis in CIT-treated cells. Our data showed that CIT increased the expression of LC3-II, an autophagosome biomarker, from the early stage of treatment (6 h). After treatment with CIT for 12 h, lysosomal membrane permeabilization occurred, followed by the release of cathepsin D in HepG2 cells. Inhibition of autophagosome formation with siRNA against Atg5 attenuated CIT-induced lysosomal membrane permeabilization. In addition, CIT induced collapse of mitochondrial transmembrane potential as assessed by JC-1 staining. Furthermore, caspase-3 activity assay showed that CIT induced apoptosis in HepG2 cells. Inhibition of autophagosome formation attenuated CIT-induced apoptosis, indicating that CIT-induced apoptosis was autophagy-dependent. Cathepsin D inhibitor, pepstatin A, relieved CIT-induced apoptosis as well, suggesting the involvement of the lysosomal-mitochondrial axis in CIT-induced apoptosis. Taken together, our data demonstrated that CIT induced autophagy-dependent apoptosis through the lysosomal-mitochondrial axis in HepG2 cells. The study thus provides essential mechanistic insight, and suggests clues for the effective management and treatment of CIT-related diseases. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6651 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07bf9e527059a36137a2716dbd9e1e14Test https://pubmed.ncbi.nlm.nih.gov/26258792Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....07bf9e527059a36137a2716dbd9e1e14 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726651 |
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