YC-1 induces lipid droplet formation in RAW 264.7 macrophages

Leo Tsui, Shwu Fen Chang, Hsiang Po Huang, Tsorng Harn Fong, I. Jong Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
JournalJournal of Biomedical Science
DOIs
Publication statusAccepted/In press - Jan 15 2016

Fingerprint

Macrophages
Lipids
Foam Cells
Foams
Guanylate Cyclase
Cyclic GMP
Cyclic GMP-Dependent Protein Kinases
Lipid Droplets
Assays
Screening
Fluorescence
Cells
Clinical Trials
Staining and Labeling
Pharmaceutical Preparations
oxidized low density lipoprotein

Keywords

  • cGMP-dependent protein kinase
  • Foam cells
  • Macrophages
  • Oxidized low density lipoproteins
  • YC-1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

YC-1 induces lipid droplet formation in RAW 264.7 macrophages. / Tsui, Leo; Chang, Shwu Fen; Huang, Hsiang Po; Fong, Tsorng Harn; Wang, I. Jong.

In: Journal of Biomedical Science, 15.01.2016.

Research output: Contribution to journalArticle

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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. Conclusion: 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.",
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