Role of downstream metabolic processing of proinflammatory fatty acids by 5-lipoxygenase in hl-60 cell apoptosis

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 μmol/L AA and an enzyme inhibitor (1-10 μmol/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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)91-103
Number of pages13
JournalJournal of Trauma
Volume54
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Arachidonate 5-Lipoxygenase
Fatty Acids
Apoptosis
Arachidonate Lipoxygenases
Prostaglandin-Endoperoxide Synthases
HL-60 Cells
Arachidonic Acid
Lipoxygenase
Necrosis
Arachidonate 12-Lipoxygenase
Lipoxygenase Inhibitors
Cyclooxygenase Inhibitors
Eicosanoids
Enzyme Inhibitors
DNA Fragmentation
Cell Survival
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

@article{d5545d40e68246e6ba59cd413f0c6f6b,
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 μmol/L AA and an enzyme inhibitor (1-10 μmol/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. Conclusion 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.",
author = "Gillis, {Robert C.} and Brian Daley and Blaine Enderson and Michael Karlstad",
year = "2003",
month = "1",
day = "1",
doi = "10.1097/00005373-200301000-00012",
language = "English (US)",
volume = "54",
pages = "91--103",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Role of downstream metabolic processing of proinflammatory fatty acids by 5-lipoxygenase in hl-60 cell apoptosis

AU - Gillis, Robert C.

AU - Daley, Brian

AU - Enderson, Blaine

AU - Karlstad, Michael

PY - 2003/1/1

Y1 - 2003/1/1

N2 - 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 μmol/L AA and an enzyme inhibitor (1-10 μmol/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. Conclusion 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.

AB - 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 μmol/L AA and an enzyme inhibitor (1-10 μmol/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. Conclusion 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.

UR - http://www.scopus.com/inward/record.url?scp=0037237249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037237249&partnerID=8YFLogxK

U2 - 10.1097/00005373-200301000-00012

DO - 10.1097/00005373-200301000-00012

M3 - Article

VL - 54

SP - 91

EP - 103

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 1

ER -