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

Yoon Sun Cho, Chih Na Yen, Joong Sup Shim, Dong Hoon Kang, Sang Won Kang, Jun O. Liu, Ho Jeong Kwon

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number34655
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Oct 3

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Ribosomal Protein S6 Kinases
Autophagy
Antidepressive Agents
Neurotransmitter Uptake Inhibitors
Smooth Muscle Myocytes
AMP-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Immunoblotting
indatraline
Dopamine
Serotonin
Norepinephrine
Cytoplasm
Observation
Electrons
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • General

Cite this

Cho, Yoon Sun ; Yen, Chih Na ; Shim, Joong Sup ; Kang, Dong Hoon ; Kang, Sang Won ; Liu, Jun O. ; Kwon, Ho Jeong. / Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway. In: Scientific reports. 2016 ; Vol. 6.
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Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway. / Cho, Yoon Sun; Yen, Chih Na; Shim, Joong Sup; Kang, Dong Hoon; Kang, Sang Won; Liu, Jun O.; Kwon, Ho Jeong.

In: Scientific reports, Vol. 6, 34655, 03.10.2016.

Research output: Contribution to journalArticle

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AU - Kang, Sang Won

AU - Liu, Jun O.

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