Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Abstract: Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tub...

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Autores principales: Hou, Xin, Xiao, Haitao, Zhang, Yanhong, Zeng, Xixi, Huang, Mengjun, Chen, Xiaoyun, Birnbaumer, Lutz, Liao, Yanhong
Formato: Artículo
Lenguaje:Inglés
Publicado: Nature Publishing Group 2019
Materias:
RIÑON
ESTRES OXIDATIVO
APOPTOSIS
CELULAS EPITELIALES
INSUFICIENCIA RENAL
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8686
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8686
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic RIÑON
ESTRES OXIDATIVO
APOPTOSIS
CELULAS EPITELIALES
INSUFICIENCIA RENAL
spellingShingle RIÑON
ESTRES OXIDATIVO
APOPTOSIS
CELULAS EPITELIALES
INSUFICIENCIA RENAL
Hou, Xin
Xiao, Haitao
Zhang, Yanhong
Zeng, Xixi
Huang, Mengjun
Chen, Xiaoyun
Birnbaumer, Lutz
Liao, Yanhong
Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
topic_facet RIÑON
ESTRES OXIDATIVO
APOPTOSIS
CELULAS EPITELIALES
INSUFICIENCIA RENAL
description Abstract: Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tubular cells (PTC), which are the main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic process that removes long-lived proteins and damaged organelles via lysosome-mediated degradation, which has an antioxidant effect that relieves oxidative stress. The canonical transient receptor potential channel 6 (TRPC6), a nonselective cation channel that allows passage of Ca2+, plays an important role in renal disease. Yet, the relationship between TRPC6 and autophagy, as well as their functions in renal oxidative stress injury, remains unclear. In this study, we found that oxidative stress triggered TRPC6-dependent Ca2+ influx in PTC to inhibit autophagy, thereby rendering cells more susceptible to death. We also demonstrated that TRPC6 knockout (TRPC6-/-) or inhibition by SAR7334, a TRPC6-selective inhibitor, increased autophagic flux and mitigated oxidative stress-induced apoptosis of PTC. The protective effects of TRPC6 ablation were prevented by autophagy inhibitors Chloroquine and Bafilomycin A1. Moreover, this study also shows that TRPC6 blockage promotes autophagic flux via inhibiting the PI3K/Akt/mTOR and ERK1/2 signaling pathways. This is the first evidence showing that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in PTC, and it may become a novel therapeutic target for the treatment of renal oxidative stress injury in the future.
format Artículo
author Hou, Xin
Xiao, Haitao
Zhang, Yanhong
Zeng, Xixi
Huang, Mengjun
Chen, Xiaoyun
Birnbaumer, Lutz
Liao, Yanhong
author_facet Hou, Xin
Xiao, Haitao
Zhang, Yanhong
Zeng, Xixi
Huang, Mengjun
Chen, Xiaoyun
Birnbaumer, Lutz
Liao, Yanhong
author_sort Hou, Xin
title Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
title_short Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
title_full Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
title_fullStr Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
title_full_unstemmed Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
title_sort transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation
publisher Nature Publishing Group
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8686
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AT zhangyanhong transientreceptorpotentialchannel6knockdownpreventsapoptosisofrenaltubularepithelialcellsuponoxidativestressviaautophagyactivation
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AT chenxiaoyun transientreceptorpotentialchannel6knockdownpreventsapoptosisofrenaltubularepithelialcellsuponoxidativestressviaautophagyactivation
AT birnbaumerlutz transientreceptorpotentialchannel6knockdownpreventsapoptosisofrenaltubularepithelialcellsuponoxidativestressviaautophagyactivation
AT liaoyanhong transientreceptorpotentialchannel6knockdownpreventsapoptosisofrenaltubularepithelialcellsuponoxidativestressviaautophagyactivation
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