title: Role of downstream metabolic processing of proinflammatory fatty acids by 5-lipoxygenase in HL-60 cell apoptosis.
abstract: BACKGROUND
  Proinflammatory eicosanoids formed from arachidonic acid (AA) by lipoxygenase (LO) and cyclooxygenase (COX) pathways have been shown to inhibit apoptosis in certain cell types. This study determined whether inhibition of LO and COX increased apoptosis in AA-treated HL-60 cells in vitro.
  
  
  METHODS
  HL-60 cells were incubated with 50 micromol/L AA and an enzyme inhibitor (1-10 micromol/L) for COX, LO, 12-LO, and 5-LO for 12 hours. Flow cytometry was used to assess viability, apoptosis, and necrosis. Apoptosis was further assessed using terminal dUTP nick end-labeling and DNA fragmentation.
  
  
  RESULTS
  The highest concentration of LO inhibitors, but not COX inhibitors, decreased viability and increased apoptosis and necrosis in the presence of exogenous AA.
  
  
  CONCLUSIONS
  These results suggest that disruption of the metabolism of AA by LO, in particular 5-LO, decreases cell survival and increases apoptosis. Thus, downstream metabolic processing of AA by LO but not COX plays a critical role in the regulation of HL-60 cell apoptosis.
authors.affiliation: Division of Trauma and Critical Care, Department of Surgery, Graduate School of Medicine, The University of Tennessee Medical Center, Knoxville, Tennessee 37920, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gillis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Daley
authors.forename: Blaine L
authors.initials: BL
authors.lastname: Enderson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Karlstad
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D016227:Benzoquinones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005395:Fish Oils / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000378:metabolism*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation; D016859:Lipoxygenase Inhibitors; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D002722:Chlorobenzenes
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D044950:Flavanones; D005419:Flavonoids; D007052:Ibuprofen; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; C060893:MK-886; D002722:Chlorobenzenes; C006680:baicalein; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone