| Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid-treated HL-60 cells. | |
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MedLine Citation:
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PMID: 15449569 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Enteral nutrition containing eicosapentaenoic (20:5 omega-3) and gamma-linolenic acid (18:3 omega-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/gamma-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. METHODS: Cells were incubated with 50 microM eicosapentaenoic/20 microM gamma-linolenic acid in the presence of an enzyme inhibitor (1-10 microM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. RESULTS: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. CONCLUSIONS: These data suggest that the processing of eicosapentaenoic and gamma-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival. |
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Authors:
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Robert C Gillis; Brian J Daley; Blaine L Enderson; Michael D Karlstad |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: JPEN. Journal of parenteral and enteral nutrition Volume: 28 ISSN: 0148-6071 ISO Abbreviation: JPEN J Parenter Enteral Nutr Publication Date: 2004 Sep-Oct |
Date Detail:
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Created Date: 2004-09-28 Completed Date: 2005-04-08 Revised Date: 2007-02-21 |
Medline Journal Info:
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Nlm Unique ID: 7804134 Medline TA: JPEN J Parenter Enteral Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 308-14 Citation Subset: IM |
Affiliation:
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Division of Trauma and Critical Care, Department of Surgery, Graduate School of Medicine, The University of Tennessee Medical Center, Knoxville, Tennessee 37920, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Arachidonate 5-Lipoxygenase / antagonists & inhibitors*, metabolism Cell Survival / drug effects Cyclooxygenase Inhibitors Dose-Response Relationship, Drug Drug Combinations Eicosapentaenoic Acid / pharmacology* Enteral Nutrition* Flow Cytometry HL-60 Cells Humans gamma-Linolenic Acid / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Drug Combinations; 1553-41-9/Eicosapentaenoic Acid; 506-26-3/gamma-Linolenic Acid; EC 1.13.11.34/Arachidonate 5-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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