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Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway
Cho Y.S.2; Yen C.-N.2; Shim J.S.5; Kang D.H.3; Kang S.W.3; Liu J.O.5; Kwon H.J.2
2016-10-03
Source PublicationScientific Reports
ISSN20452322
Volume6
AbstractIndatraline 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.
DOI10.1038/srep34655
URLView the original
Language英語
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Yonsei University College of Medicine
2.Yonsei University
3.Ewha Womans University
4.Universidade de Macau
5.The Johns Hopkins School of Medicine
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GB/T 7714
Cho Y.S.,Yen C.-N.,Shim J.S.,et al. Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway[J]. Scientific Reports,2016,6.
APA Cho Y.S..,Yen C.-N..,Shim J.S..,Kang D.H..,Kang S.W..,...&Kwon H.J..(2016).Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway.Scientific Reports,6.
MLA Cho Y.S.,et al."Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway".Scientific Reports 6(2016).
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