A novel antioxidant Mito-Tempol inhibits ox-LDL-induced foam cell formation through restoration of autophagy flux

doi:10.1016/j.freeradbiomed.2018.10.412

	A novel antioxidant Mito-Tempol inhibits ox-LDL-induced foam cell formation through restoration of autophagy flux
	Ma, Ying 5; Huang, Zhenyu 4; Zhou, Zhaoli 1,3; He, Xiaoyan 1,3; Wang, Ying 2; Meng, Chao 5; Huang, Gang 3; Fang, Ningyuan 5
刊名	FREE RADICAL BIOLOGY AND MEDICINE
	2018-12
卷号	129 页码:463-472
关键词	Mito-Tempol Atherosclerosis Autophagy Oxidative stress Macrophage Foam cells
ISSN号	0891-5849
DOI	10.1016/j.freeradbiomed.2018.10.412
文献子类	Article
英文摘要	A bulk of cholesteryl esters accumulation in macrophage foam cells drives the occurrence and development of atherosclerosis. Evidence now shows that autophagy plays key roles in the degradation of intracellular lipid droplets via autolysosome, and also in the release of intracellular lipids via cholesterol efflux. In this study, we identified that a mitochondria-targeted antioxidant, Mito-Tempol, has protective effects against cholesteryl esters accumulation by activating autophagy. Mito-Tempol was shown to ameliorate the lipid burden for atherosclerosis, both in vitro and in vivo. In the established in vitro foam cell formation system using oxidized low-density lipoprotein (ox-LDL)-loaded THP-1 macrophages, Mito-Tempol prevented intracellular oxidative stress and attenuated lipid accumulation. Mito-Tempol rescued ox-LDL-impaired autophagic flux, thereby facilitating autophagy-mediated lipid degradation in THP-1 macrophages. Meanwhile, Mito-Tempol also increased the efflux of cholesterol via autophagy-dependent ABCA1 and ABCG1 up-regulation. The classical autophagy pathway of mTOR may be one of the effector for the autophagy restoration of Mito-Tempol. Our findings give the first insight that cardiovascular system disease may benefits more from the treatment of Mito-Tempol for its impact of reversing atherosclerosis via autophagy.
资助项目	National Natural Science Foundation of China[81370360]
WOS关键词	LOW-DENSITY-LIPOPROTEIN ; SUPEROXIDE-DISMUTASE ; PHOTODYNAMIC THERAPY ; CHOLESTEROL EFFLUX ; GENE-EXPRESSION ; REACTIVE OXYGEN ; MACROPHAGE ; ATHEROSCLEROSIS ; ACTIVATION ; PTEN
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000450298400043
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279482]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Fang, Ningyuan
作者单位	1.Shanghai Univ Med & Hlth Sci, Sch Pharm, Dept Pharmacol, Shanghai 200093, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Shanghai Univ Med & Hlth Sci, Collaborat Sci Res Ctr, Shanghai Key Lab Mol Imaging, Shanghai 200093, Peoples R China; 4.Second Millitary Med Univ, Changzheng Hosp Shanghai, Dept Neurosurg, Shanghai 200003, Peoples R China; 5.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Geriatr, Shanghai 200127, Peoples R China;
推荐引用方式 GB/T 7714	Ma, Ying,Huang, Zhenyu,Zhou, Zhaoli,et al. A novel antioxidant Mito-Tempol inhibits ox-LDL-induced foam cell formation through restoration of autophagy flux[J]. FREE RADICAL BIOLOGY AND MEDICINE,2018,129:463-472.
APA	Ma, Ying.,Huang, Zhenyu.,Zhou, Zhaoli.,He, Xiaoyan.,Wang, Ying.,...&Fang, Ningyuan.(2018).A novel antioxidant Mito-Tempol inhibits ox-LDL-induced foam cell formation through restoration of autophagy flux.FREE RADICAL BIOLOGY AND MEDICINE,129,463-472.
MLA	Ma, Ying,et al."A novel antioxidant Mito-Tempol inhibits ox-LDL-induced foam cell formation through restoration of autophagy flux".FREE RADICAL BIOLOGY AND MEDICINE 129(2018):463-472.