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Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes

Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemic...

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Autores principales: Makino, Asami, Hullin-Matsuda, Françoise, Murate, Motohide, Abe, Mitsuhiro, Tomishige, Nario, Fukuda, Mitsunori, Yamashita, Shizuya, Fujimoto, Toyoshi, Vidal, Hubert, Lagarde, Michel, Delton, Isabelle, Kobayashi, Toshihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170862/
https://www.ncbi.nlm.nih.gov/pubmed/27582390
http://dx.doi.org/10.1091/mbc.E15-10-0730
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author Makino, Asami
Hullin-Matsuda, Françoise
Murate, Motohide
Abe, Mitsuhiro
Tomishige, Nario
Fukuda, Mitsunori
Yamashita, Shizuya
Fujimoto, Toyoshi
Vidal, Hubert
Lagarde, Michel
Delton, Isabelle
Kobayashi, Toshihide
author_facet Makino, Asami
Hullin-Matsuda, Françoise
Murate, Motohide
Abe, Mitsuhiro
Tomishige, Nario
Fukuda, Mitsunori
Yamashita, Shizuya
Fujimoto, Toyoshi
Vidal, Hubert
Lagarde, Michel
Delton, Isabelle
Kobayashi, Toshihide
author_sort Makino, Asami
collection PubMed
description Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemical properties of lipid droplets (LDs) in cultured hepatocytes. Acute free cholesterol accumulation induced the fusion of LDs, followed by degradation of the coat protein of LDs, perilipin 2 (PLIN2; also called adipophilin or adipose differentiation–related protein), and association of apolipoprotein B 100 (ApoB 100) to LDs. The degradation of PLIN2 was inhibited by inhibitors of ubiquitination, autophagy, and protein synthesis. The results indicate that association of ApoB 100 with LDs is dependent on the activity of low–molecular weight GTP-binding protein Rab18 and highlight the role of LDs as targets of free cholesterol toxicity in hepatocytes.
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spelling pubmed-51708622017-01-16 Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes Makino, Asami Hullin-Matsuda, Françoise Murate, Motohide Abe, Mitsuhiro Tomishige, Nario Fukuda, Mitsunori Yamashita, Shizuya Fujimoto, Toyoshi Vidal, Hubert Lagarde, Michel Delton, Isabelle Kobayashi, Toshihide Mol Biol Cell Articles Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemical properties of lipid droplets (LDs) in cultured hepatocytes. Acute free cholesterol accumulation induced the fusion of LDs, followed by degradation of the coat protein of LDs, perilipin 2 (PLIN2; also called adipophilin or adipose differentiation–related protein), and association of apolipoprotein B 100 (ApoB 100) to LDs. The degradation of PLIN2 was inhibited by inhibitors of ubiquitination, autophagy, and protein synthesis. The results indicate that association of ApoB 100 with LDs is dependent on the activity of low–molecular weight GTP-binding protein Rab18 and highlight the role of LDs as targets of free cholesterol toxicity in hepatocytes. The American Society for Cell Biology 2016-11-01 /pmc/articles/PMC5170862/ /pubmed/27582390 http://dx.doi.org/10.1091/mbc.E15-10-0730 Text en © 2016 Makino et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Makino, Asami
Hullin-Matsuda, Françoise
Murate, Motohide
Abe, Mitsuhiro
Tomishige, Nario
Fukuda, Mitsunori
Yamashita, Shizuya
Fujimoto, Toyoshi
Vidal, Hubert
Lagarde, Michel
Delton, Isabelle
Kobayashi, Toshihide
Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title_full Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title_fullStr Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title_full_unstemmed Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title_short Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes
title_sort acute accumulation of free cholesterol induces the degradation of perilipin 2 and rab18-dependent fusion of er and lipid droplets in cultured human hepatocytes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170862/
https://www.ncbi.nlm.nih.gov/pubmed/27582390
http://dx.doi.org/10.1091/mbc.E15-10-0730
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