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Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an im...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320537/ https://www.ncbi.nlm.nih.gov/pubmed/28225005 http://dx.doi.org/10.1038/srep42764 |
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author | Jiang, Xu-shun Chen, Xue-mei Wan, Jiang-min Gui, Hai-bo Ruan, Xiong-zhong Du, Xiao-gang |
author_facet | Jiang, Xu-shun Chen, Xue-mei Wan, Jiang-min Gui, Hai-bo Ruan, Xiong-zhong Du, Xiao-gang |
author_sort | Jiang, Xu-shun |
collection | PubMed |
description | Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis. |
format | Online Article Text |
id | pubmed-5320537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53205372017-03-01 Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro Jiang, Xu-shun Chen, Xue-mei Wan, Jiang-min Gui, Hai-bo Ruan, Xiong-zhong Du, Xiao-gang Sci Rep Article Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis. Nature Publishing Group 2017-02-22 /pmc/articles/PMC5320537/ /pubmed/28225005 http://dx.doi.org/10.1038/srep42764 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Jiang, Xu-shun Chen, Xue-mei Wan, Jiang-min Gui, Hai-bo Ruan, Xiong-zhong Du, Xiao-gang Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title | Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title_full | Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title_fullStr | Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title_full_unstemmed | Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title_short | Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro |
title_sort | autophagy protects against palmitic acid-induced apoptosis in podocytes in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320537/ https://www.ncbi.nlm.nih.gov/pubmed/28225005 http://dx.doi.org/10.1038/srep42764 |
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