Cargando…

Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells

Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptide...

Descripción completa

Detalles Bibliográficos
Autores principales: Hao, Shuangying, Ji, Jiajie, Zhao, Hongting, Shang, Longcheng, Wu, Jing, Li, Huihui, Qiao, Tong, Li, Kuanyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332157/
https://www.ncbi.nlm.nih.gov/pubmed/26633327
http://dx.doi.org/10.3390/molecules201219764
_version_ 1783387284202061824
author Hao, Shuangying
Ji, Jiajie
Zhao, Hongting
Shang, Longcheng
Wu, Jing
Li, Huihui
Qiao, Tong
Li, Kuanyu
author_facet Hao, Shuangying
Ji, Jiajie
Zhao, Hongting
Shang, Longcheng
Wu, Jing
Li, Huihui
Qiao, Tong
Li, Kuanyu
author_sort Hao, Shuangying
collection PubMed
description Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis.
format Online
Article
Text
id pubmed-6332157
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63321572019-01-24 Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells Hao, Shuangying Ji, Jiajie Zhao, Hongting Shang, Longcheng Wu, Jing Li, Huihui Qiao, Tong Li, Kuanyu Molecules Article Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis. MDPI 2015-12-01 /pmc/articles/PMC6332157/ /pubmed/26633327 http://dx.doi.org/10.3390/molecules201219764 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hao, Shuangying
Ji, Jiajie
Zhao, Hongting
Shang, Longcheng
Wu, Jing
Li, Huihui
Qiao, Tong
Li, Kuanyu
Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title_full Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title_fullStr Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title_full_unstemmed Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title_short Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
title_sort mitochondrion-targeted peptide ss-31 inhibited oxidized low-density lipoproteins-induced foam cell formation through both ros scavenging and inhibition of cholesterol influx in raw264.7 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332157/
https://www.ncbi.nlm.nih.gov/pubmed/26633327
http://dx.doi.org/10.3390/molecules201219764
work_keys_str_mv AT haoshuangying mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT jijiajie mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT zhaohongting mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT shanglongcheng mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT wujing mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT lihuihui mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT qiaotong mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells
AT likuanyu mitochondriontargetedpeptidess31inhibitedoxidizedlowdensitylipoproteinsinducedfoamcellformationthroughbothrosscavengingandinhibitionofcholesterolinfluxinraw2647cells