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 journalArticlepeer-review

12 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

Bibliographical note

Funding Information:
We are grateful to Tamotsu Yoshimori for plasmid encoding EGFP-LC3 and the anti-LC3 antibody. This work was partly supported by grants from the National Research Foundation of Korea, funded by the Korean government (MSIP; 2015K1A1A2028365, 2015M3A9B6027818, 2015M3A9C4676321, 2012M3A9D1054520) and the Brain Korea 21 Plus Project, Republic of Korea. Yoon Sun Cho is supported by the Future Basic Science Research Leader Training Program from NRF.

All Science Journal Classification (ASJC) codes

  • General

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