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Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway

Title
Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway
Authors
Cho, Yoon SunYen, Chih-naShim, Joong SupKang, Dong HoonKang, Sang WonLiu, Jun O.Kwon, Ho Jeong
Ewha Authors
강상원강동훈
SCOPUS Author ID
강상원scopus; 강동훈scopus
Issue Date
2016
Journal Title
SCIENTIFIC REPORTS
ISSN
2045-2322JCR Link
Citation
SCIENTIFIC REPORTS vol. 6
Publisher
NATURE PUBLISHING GROUP
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Indatraline is an antidepressive agent and a non-selective monoamine transporter inhibitor that blocks the reuptake of neurotransmitters (dopamine, serotonin, and norepinephrine). In this study, we report that indatraline induces autophagy via the suppression of mTOR/S6 kinase signaling. Autophagy induction was examined by a cell-based high content screening system using LysoTracker, which was followed by monodansylcadaverine staining and transmission electron microscope observation. Indatraline increased the number of EGFP-LC3 cells expressing autophagosomes in the cytoplasm. Conversion of LC3 was further validated by immunoblotting. Indatraline induced autophagy by affecting the AMPK/mTOR/S6K signaling axis and had no influence on the PI3K/AKT/ERK signaling. Moreover, indatraline induced autophagy in smooth muscle cells (SMCs); further, it exhibited therapeutic potential for restenosis by inhibiting SMC accumulation in a rat restenosis model. These results provide new insights into the role of monoamine transporters in autophagy regulation and identify indatraline as a novel agent for inducing autophagy.
DOI
10.1038/srep34655
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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