Increased Δ5- and Δ6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis

Sarah W. Njoroge, Adam C. Seegmiller, Waddah Katrangi, Michael Laposata

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Patients with cystic fibrosis consistently demonstrate selective abnormalities in essential fatty acid concentrations, including decreased linoleate (LA) and docosahexaenoate (DHA), with variably increased arachidonate (AA). These changes appear important for the pathophysiology of the disease. However, the mechanisms of these changes are not clearly understood. The current study demonstrates that metabolism of LA and alpha linolenate (LNA) to AA and eicosapentaenoate (EPA), respectively, are significantly increased in two different cell culture models of cystic fibrosis. These changes correlated with increased expression of fatty acid Δ5- and Δ6-desaturases, key enzymes in this metabolic pathway. In contrast, cystic fibrosis cells showed decreased metabolism of AA and EPA to docosapentaenoate (DPA) and docosahexaenoate (DHA), respectively, although metabolism of 22:5n-3 to DHA was relatively unchanged. In addition, the expression and activity of both cyclooxygenase-2 and lipoxygenase-5 was markedly increased in these cells. Taken together, these findings are consistent with the conclusion that the diminished LA and increased AA in cystic fibrosis result from increased metabolism of LA, while the observed decrease in DHA is at least partly due to decreased elongation and desaturation beyond EPA.

Original languageEnglish (US)
Pages (from-to)431-440
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1811
Issue number7-8
DOIs
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Arachidonate 5-Lipoxygenase
Eicosanoids
Docosahexaenoic Acids
Linoleic Acid
Cyclooxygenase 2
Cystic Fibrosis
Fatty Acids
Essential Fatty Acids
alpha-Linolenic Acid
Metabolic Networks and Pathways
Cell Culture Techniques
Enzymes

Keywords

  • Cyclooxygenase
  • Cystic fibrosis
  • Desaturase
  • Eicosanoid
  • Fatty acid
  • Lipoxygenase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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title = "Increased Δ5- and Δ6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis",
abstract = "Patients with cystic fibrosis consistently demonstrate selective abnormalities in essential fatty acid concentrations, including decreased linoleate (LA) and docosahexaenoate (DHA), with variably increased arachidonate (AA). These changes appear important for the pathophysiology of the disease. However, the mechanisms of these changes are not clearly understood. The current study demonstrates that metabolism of LA and alpha linolenate (LNA) to AA and eicosapentaenoate (EPA), respectively, are significantly increased in two different cell culture models of cystic fibrosis. These changes correlated with increased expression of fatty acid Δ5- and Δ6-desaturases, key enzymes in this metabolic pathway. In contrast, cystic fibrosis cells showed decreased metabolism of AA and EPA to docosapentaenoate (DPA) and docosahexaenoate (DHA), respectively, although metabolism of 22:5n-3 to DHA was relatively unchanged. In addition, the expression and activity of both cyclooxygenase-2 and lipoxygenase-5 was markedly increased in these cells. Taken together, these findings are consistent with the conclusion that the diminished LA and increased AA in cystic fibrosis result from increased metabolism of LA, while the observed decrease in DHA is at least partly due to decreased elongation and desaturation beyond EPA.",
keywords = "Cyclooxygenase, Cystic fibrosis, Desaturase, Eicosanoid, Fatty acid, Lipoxygenase",
author = "Njoroge, {Sarah W.} and Seegmiller, {Adam C.} and Waddah Katrangi and Michael Laposata",
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T1 - Increased Δ5- and Δ6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis

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AU - Seegmiller, Adam C.

AU - Katrangi, Waddah

AU - Laposata, Michael

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