title: Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux.
abstract: Our previous studies have indicated that a novel curcumin derivate nicotinate-curcumin (NC) has beneficial effects on the prevention of atherosclerosis, but the precise mechanisms are not fully understood. Given that autophagy regulates lipid metabolism, the present study was designed to investigate whether NC decreases foam cell formation through restoring autophagy flux in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells. Our results showed that ox-LDL (100 μg/ml) was accumulated in THP-1 cells and impaired autophagy flux. Ox-LDL-induced impairment of autophagy was enhanced by treatment with the autophagy inhibitor chloroquine (CQ) and rescued by the autophagy inducer rapamycin. The aggregation of ox-LDL was increased by CQ, but decreased by rapamycin. In addition, colocalization of lipid droplets with LC3-II was remarkably reduced in ox-LDL group. In contrast, NC (10 μM) rescued the impaired autophagy flux by significantly increasing level of LC3-II, the number of autophagolysosomes, and the degradation of p62 in ox-LDL-treated THP-1 cells. Inhibition of the PI3K-Akt-mTOR signaling was required for NC-rescued autophagy flux. Notably, our results showed that NC remarkably promoted the colocalization of lipid droplets with autophagolysosomes, increased efflux of cholesterol, and reduced ox-LDL accumulation in THP-1 cells. However, treatment with 3-methyladenine (3-MA) or CQ reduced the protective effects of NC on lipid accumulation. Collectively, the findings suggest that NC decreases lipid accumulation in THP-1 cells through restoring autophagy flux, and further implicate that NC may be a potential therapeutic reagent to reverse atherosclerosis.
authors.affiliation: Department of Physiology, University of South China, Hengyang, People's Republic of China.|Institute of Neuroscience, University of South China, Hengyang, People's Republic of China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, People's Republic of China.
authors.forename: Hai-Zhe
authors.initials: HZ
authors.lastname: Li
authors.affiliation: Department of Physiology, University of South China, Hengyang, People's Republic of China.|Institute of Neuroscience, University of South China, Hengyang, People's Republic of China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Tang
authors.affiliation: Department of Physiology, University of South China, Hengyang, People's Republic of China.|Institute of Neuroscience, University of South China, Hengyang, People's Republic of China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
authors.affiliation: Smooth Muscle Research Group, Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.|Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005487:Foam Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009525:Niacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000225:Adenine; D002738:Chloroquine; D002784:Cholesterol; D003474:Curcumin; D008077:Lipoproteins, LDL; D009525:Niacin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C000718064:curcumin nicotinate; C099252:oxidized low density lipoprotein; C025946:3-methyladenine; C546842:MTOR protein, human