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Title: Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line

Abstract

Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis. We found that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra, induced lipid accumulation, a phenotype associated with quiescent HSCs, through blockade of autophagy in the rat-derived HSC line HSC-T6. Tetrandrine inhibited autophagic flux without affecting lysosomal function. A phenotypic comparison using siRNA knockdown suggested that tetrandrine may target regulators, involved in fusion between autophagosomes and lysosomes (e.g., syntaxin 17). Moreover, perilipin 1, an LD-coated protein, co-localized specifically with LC3, a marker protein for autophagosomes, in tetrandrine-treated HSC-T6 cells. This suggests a potential role for perilipin 1 in autophagy-mediated LD degradation in HSCs. Our results identified tetrandrine as a potential tool for prevention and treatment of HSC activation. - Highlights: • Autophagy is closely related to lipid degradation in hepatic stellate cells. • Tetrandrine (Tet) causes lipid accumulationmore » via blockade of autophagy in HSC-T6 cells. • Tet blocked autophagy without affecting lysosomal function unlike bafilomycin A{sub 1}. • Perilipin 1 was specifically co-localized with LC3 in Tet-treated cells. • Perilipin 1 may play potential roles in autophagy-mediated lipid degradation.« less

Authors:
 [1]; ;  [1]; ;  [2]; ;  [1];  [1]
  1. Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan)
  2. Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki 305-8572 (Japan)
Publication Date:
OSTI Identifier:
22606145
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 477; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKALOIDS; CELL CONSTITUENTS; FIBROSIS; GENES; INHIBITION; LIPIDS; LIVER; LYSOSOMES; PATHOGENESIS; PHENOTYPE; PROTEINS; RATS

Citation Formats

Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp, Nishito, Yukina, Nakai, Naomi, Nagumo, Yoko, Usui, Takeo, Masuda, Seiji, Kambe, Taiho, and Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp. Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.06.018.
Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp, Nishito, Yukina, Nakai, Naomi, Nagumo, Yoko, Usui, Takeo, Masuda, Seiji, Kambe, Taiho, & Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp. Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line. United States. doi:10.1016/J.BBRC.2016.06.018.
Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp, Nishito, Yukina, Nakai, Naomi, Nagumo, Yoko, Usui, Takeo, Masuda, Seiji, Kambe, Taiho, and Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp. Fri . "Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line". United States. doi:10.1016/J.BBRC.2016.06.018.
@article{osti_22606145,
title = {Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line},
author = {Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp and Nishito, Yukina and Nakai, Naomi and Nagumo, Yoko and Usui, Takeo and Masuda, Seiji and Kambe, Taiho and Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp},
abstractNote = {Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis. We found that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra, induced lipid accumulation, a phenotype associated with quiescent HSCs, through blockade of autophagy in the rat-derived HSC line HSC-T6. Tetrandrine inhibited autophagic flux without affecting lysosomal function. A phenotypic comparison using siRNA knockdown suggested that tetrandrine may target regulators, involved in fusion between autophagosomes and lysosomes (e.g., syntaxin 17). Moreover, perilipin 1, an LD-coated protein, co-localized specifically with LC3, a marker protein for autophagosomes, in tetrandrine-treated HSC-T6 cells. This suggests a potential role for perilipin 1 in autophagy-mediated LD degradation in HSCs. Our results identified tetrandrine as a potential tool for prevention and treatment of HSC activation. - Highlights: • Autophagy is closely related to lipid degradation in hepatic stellate cells. • Tetrandrine (Tet) causes lipid accumulation via blockade of autophagy in HSC-T6 cells. • Tet blocked autophagy without affecting lysosomal function unlike bafilomycin A{sub 1}. • Perilipin 1 was specifically co-localized with LC3 in Tet-treated cells. • Perilipin 1 may play potential roles in autophagy-mediated lipid degradation.},
doi = {10.1016/J.BBRC.2016.06.018},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 477,
place = {United States},
year = {Fri Aug 12 00:00:00 EDT 2016},
month = {Fri Aug 12 00:00:00 EDT 2016}
}