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Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells

Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of au...

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Autores principales: Kim, Eun Sung, Shin, Ji Hyun, Park, So Jung, Jo, Yoon Kyung, Kim, Jae-Sung, Kang, Il-Hwan, Nam, Jung-Bum, Chung, Doo-Young, Cho, Yoonchul, Lee, EunJoo H., Chang, Jong Wook, Cho, Dong-Hyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324942/
https://www.ncbi.nlm.nih.gov/pubmed/25671433
http://dx.doi.org/10.1371/journal.pone.0118190
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author Kim, Eun Sung
Shin, Ji Hyun
Park, So Jung
Jo, Yoon Kyung
Kim, Jae-Sung
Kang, Il-Hwan
Nam, Jung-Bum
Chung, Doo-Young
Cho, Yoonchul
Lee, EunJoo H.
Chang, Jong Wook
Cho, Dong-Hyung
author_facet Kim, Eun Sung
Shin, Ji Hyun
Park, So Jung
Jo, Yoon Kyung
Kim, Jae-Sung
Kang, Il-Hwan
Nam, Jung-Bum
Chung, Doo-Young
Cho, Yoonchul
Lee, EunJoo H.
Chang, Jong Wook
Cho, Dong-Hyung
author_sort Kim, Eun Sung
collection PubMed
description Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.
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spelling pubmed-43249422015-02-18 Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells Kim, Eun Sung Shin, Ji Hyun Park, So Jung Jo, Yoon Kyung Kim, Jae-Sung Kang, Il-Hwan Nam, Jung-Bum Chung, Doo-Young Cho, Yoonchul Lee, EunJoo H. Chang, Jong Wook Cho, Dong-Hyung PLoS One Research Article Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis. Public Library of Science 2015-02-11 /pmc/articles/PMC4324942/ /pubmed/25671433 http://dx.doi.org/10.1371/journal.pone.0118190 Text en © 2015 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kim, Eun Sung
Shin, Ji Hyun
Park, So Jung
Jo, Yoon Kyung
Kim, Jae-Sung
Kang, Il-Hwan
Nam, Jung-Bum
Chung, Doo-Young
Cho, Yoonchul
Lee, EunJoo H.
Chang, Jong Wook
Cho, Dong-Hyung
Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title_full Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title_fullStr Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title_full_unstemmed Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title_short Inhibition of Autophagy Suppresses Sertraline-Mediated Primary Ciliogenesis in Retinal Pigment Epithelium Cells
title_sort inhibition of autophagy suppresses sertraline-mediated primary ciliogenesis in retinal pigment epithelium cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324942/
https://www.ncbi.nlm.nih.gov/pubmed/25671433
http://dx.doi.org/10.1371/journal.pone.0118190
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