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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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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. |
format | Online Article Text |
id | pubmed-5170862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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