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Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells

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 i...

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Autores principales: Wang, Yuexia, Liu, Yanan, Liu, Xiaofang, Jiang, Liping, Yang, Guang, Sun, Xiance, Geng, Chengyan, Li, Qiujuan, Yao, Xiaofeng, Chen, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549738/
https://www.ncbi.nlm.nih.gov/pubmed/26258792
http://dx.doi.org/10.3390/toxins7083030
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author Wang, Yuexia
Liu, Yanan
Liu, Xiaofang
Jiang, Liping
Yang, Guang
Sun, Xiance
Geng, Chengyan
Li, Qiujuan
Yao, Xiaofeng
Chen, Min
author_facet Wang, Yuexia
Liu, Yanan
Liu, Xiaofang
Jiang, Liping
Yang, Guang
Sun, Xiance
Geng, Chengyan
Li, Qiujuan
Yao, Xiaofeng
Chen, Min
author_sort Wang, Yuexia
collection PubMed
description 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.
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spelling pubmed-45497382015-08-31 Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells Wang, Yuexia Liu, Yanan Liu, Xiaofang Jiang, Liping Yang, Guang Sun, Xiance Geng, Chengyan Li, Qiujuan Yao, Xiaofeng Chen, Min Toxins (Basel) Article 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. MDPI 2015-08-06 /pmc/articles/PMC4549738/ /pubmed/26258792 http://dx.doi.org/10.3390/toxins7083030 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yuexia
Liu, Yanan
Liu, Xiaofang
Jiang, Liping
Yang, Guang
Sun, Xiance
Geng, Chengyan
Li, Qiujuan
Yao, Xiaofeng
Chen, Min
Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title_full Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title_fullStr Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title_full_unstemmed Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title_short Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis in Human Liver HepG2 Cells
title_sort citreoviridin induces autophagy-dependent apoptosis through lysosomal-mitochondrial axis in human liver hepg2 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549738/
https://www.ncbi.nlm.nih.gov/pubmed/26258792
http://dx.doi.org/10.3390/toxins7083030
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