Cargando…

Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages

There is a growing body of evidence that excess lipids, hypoxic stress and other inflammatory signals can stimulate endoplasmic reticulum (ER) stress in metabolic diseases. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study i...

Descripción completa

Detalles Bibliográficos
Autores principales: Park, Sin-Hye, Shin, Daekeun, Lim, Soon Sung, Lee, Jae-Yong, Kang, Young-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198214/
https://www.ncbi.nlm.nih.gov/pubmed/25333946
http://dx.doi.org/10.1371/journal.pone.0110581
_version_ 1782339712239796224
author Park, Sin-Hye
Shin, Daekeun
Lim, Soon Sung
Lee, Jae-Yong
Kang, Young-Hee
author_facet Park, Sin-Hye
Shin, Daekeun
Lim, Soon Sung
Lee, Jae-Yong
Kang, Young-Hee
author_sort Park, Sin-Hye
collection PubMed
description There is a growing body of evidence that excess lipids, hypoxic stress and other inflammatory signals can stimulate endoplasmic reticulum (ER) stress in metabolic diseases. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study investigated that 50 ng/ml oxidized LDL promoted unfolded protein response (UPR) and ER stress in J774A1 murine macrophages, which was blocked by extracts (PPE) of purple Perilla frutescens, a plant of the mint family Lamiaceae. The ER stressor tunicamycin was employed as a positive control. Treating 1–10 µg/ml oxidized LDL for 24 h elicited lipotoxic apoptosis in macrophages with obvious nuclear condensation and DNA fragmentation, which was inhibited by PPE. Tunicamycin and oxidized LDL activated and induced the UPR components of activating transcription factor 6 and ER resident chaperone BiP/Grp78 in temporal manners and such effects were blocked by ≥5 µg/ml PPE. In addition, PPE suppressed the enhanced mRNA transcription and splicing of X-box binding protein 1 (XBP1) by tunicamycin and oxidized LDL. The protein induction and nuclear translocation of XBP1 were deterred in PPE-treated macrophages under ER stress. The induction of ATP-binding cassette transporter A1 (ABCA1), scavenger receptor-B1 (SR-B1) and intracellular adhesion molecule-1 (ICAM-1) was abolished by the ER stressor in activated macrophages. The protein induction of ABCA1 and ICAM1 but not SR-B1 was retrieved by adding 10 µg/ml PPE to cells. These results demonstrate that PPE inhibited lipotoxic apoptosis and demoted the induction and activation of UPR components in macrophages. PPE restored normal proteostasis in activated macrophages oxidized LDL. Therefore, PPE was a potent agent antagonizing macrophage ER stress due to lipotoxic signals associated with atherosclerosis.
format Online
Article
Text
id pubmed-4198214
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41982142014-10-21 Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages Park, Sin-Hye Shin, Daekeun Lim, Soon Sung Lee, Jae-Yong Kang, Young-Hee PLoS One Research Article There is a growing body of evidence that excess lipids, hypoxic stress and other inflammatory signals can stimulate endoplasmic reticulum (ER) stress in metabolic diseases. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study investigated that 50 ng/ml oxidized LDL promoted unfolded protein response (UPR) and ER stress in J774A1 murine macrophages, which was blocked by extracts (PPE) of purple Perilla frutescens, a plant of the mint family Lamiaceae. The ER stressor tunicamycin was employed as a positive control. Treating 1–10 µg/ml oxidized LDL for 24 h elicited lipotoxic apoptosis in macrophages with obvious nuclear condensation and DNA fragmentation, which was inhibited by PPE. Tunicamycin and oxidized LDL activated and induced the UPR components of activating transcription factor 6 and ER resident chaperone BiP/Grp78 in temporal manners and such effects were blocked by ≥5 µg/ml PPE. In addition, PPE suppressed the enhanced mRNA transcription and splicing of X-box binding protein 1 (XBP1) by tunicamycin and oxidized LDL. The protein induction and nuclear translocation of XBP1 were deterred in PPE-treated macrophages under ER stress. The induction of ATP-binding cassette transporter A1 (ABCA1), scavenger receptor-B1 (SR-B1) and intracellular adhesion molecule-1 (ICAM-1) was abolished by the ER stressor in activated macrophages. The protein induction of ABCA1 and ICAM1 but not SR-B1 was retrieved by adding 10 µg/ml PPE to cells. These results demonstrate that PPE inhibited lipotoxic apoptosis and demoted the induction and activation of UPR components in macrophages. PPE restored normal proteostasis in activated macrophages oxidized LDL. Therefore, PPE was a potent agent antagonizing macrophage ER stress due to lipotoxic signals associated with atherosclerosis. Public Library of Science 2014-10-15 /pmc/articles/PMC4198214/ /pubmed/25333946 http://dx.doi.org/10.1371/journal.pone.0110581 Text en © 2014 Park et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Park, Sin-Hye
Shin, Daekeun
Lim, Soon Sung
Lee, Jae-Yong
Kang, Young-Hee
Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title_full Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title_fullStr Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title_full_unstemmed Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title_short Purple Perilla Extracts Allay ER Stress in Lipid-Laden Macrophages
title_sort purple perilla extracts allay er stress in lipid-laden macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198214/
https://www.ncbi.nlm.nih.gov/pubmed/25333946
http://dx.doi.org/10.1371/journal.pone.0110581
work_keys_str_mv AT parksinhye purpleperillaextractsallayerstressinlipidladenmacrophages
AT shindaekeun purpleperillaextractsallayerstressinlipidladenmacrophages
AT limsoonsung purpleperillaextractsallayerstressinlipidladenmacrophages
AT leejaeyong purpleperillaextractsallayerstressinlipidladenmacrophages
AT kangyounghee purpleperillaextractsallayerstressinlipidladenmacrophages