title: YC-1 induces lipid droplet formation in RAW 264.7 macrophages.
abstract: BACKGROUND
  3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) is a potential anticancer drug that may activate soluble guanylyl cyclase (sGC) and increase the level of cyclic guanosine monophosphate (cGMP). The aim of this study was to explore the effects of YC-1 on lipid droplet accumulation and foam cell formation in macrophages.
  
  
  RESULTS
  Human-oxidized low density lipoprotein (ox-LDL) was used to induce accumulation of lipid droplets in a murine macrophage cell line, RAW 264.7. Oil red O staining showed that treatment with 20 μM YC-1 for 24 h increased the area of intracellular lipid droplets in macrophages. The results of high content screening (HCS) with the AdipoRed™ assay further revealed that YC-1 enhanced ox-LDL-induced foam cell formation. This was evidenced by an increase in the total area of lipid droplets and the mean fluorescence intensity per cell. Inhibition of cGMP-dependent protein kinase (PKG) using KT5823 significantly reduced YC-1-enhanced lipid droplet formation in ox-LDL-induced macrophage foam cells.
  
  
  CONCLUSIONS
  YC-1 induces lipid droplet formation in macrophages, possibly through the sGC/cGMP/PKG signaling pathway. This chemical should be tested with caution in future clinical trials.
authors.affiliation: Department of Ophthalmology, National Taiwan University Hospital, Taipei, 100, Taiwan.
authors.forename: Leo
authors.initials: L
authors.lastname: Tsui
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsiang-Po
authors.initials: HP
authors.lastname: Huang
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. thfong@tmu.edu.tw.
authors.forename: Tsorng-Harn
authors.initials: TH
authors.lastname: Fong
authors.affiliation: Department of Ophthalmology, National Taiwan University Hospital, Taipei, 100, Taiwan. ijong@ms8.hinet.net.
authors.forename: I-Jong
authors.initials: IJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D066292:Lipid Droplets / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D015290:Second Messenger Systems / Q000187:drug effects*
chemical_list: D007191:Indazoles; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D006152:Cyclic GMP