Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients

Mauro Maccarrone, Massimo Taccone-Gallucci, Carlo Meloni, Nella Cococcetta, Simone Manca Di Villahermosa, Carlo U. Casciani, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticle

Abstract

Lipid peroxidation was shown at the membrane level in peripheral blood cells of patients hemodialyzed on cuprophan dialyzers, and was mainly attributable to the generation of conjugated hydroperoxides in the lipid bilayer. The oxidative index (i.e., the A234/205 ratio) of membrane lipids was 3.2-fold higher in hemodialysis patients than in healthy control subjects, and also the level of leukotriene B4 was significantly increased (up to 1.7-fold over control). Both membrane peroxidation and release of leukotriene B4 were linked to upregulation of 5-lipoxygenase activity (up to 2.4-fold over control) and expression at the protein level (up to 1.9-fold). Vitamin E, the most important lipophilic antioxidant, prevented both membrane peroxidation and release of leukotriene B4 by inhibiting 5-lipoxygenase activity without affecting enzyme expression. Similar results were observed in patients hemodialyzed on polymethylmetacrylate membranes, but in this case the activation of 5-lipoxygenase was less pronounced. The use of a purified 5-lipoxygenase demonstrated that vitamin E was a reversible inhibitor of enzyme activity (IC50 = 35 ± 4 μM), further characterized as noncompetitive (Ki = 30 ± 3 μM). Taken together, the results reported here shed some light on the mechanism responsible for the oxidative damage in hemodialysis. Moreover, the beneficial effect of vitamin E described here may have relevance for the therapy of patients with kidney disease.

Original languageEnglish
Pages (from-to)1991-1996
Number of pages6
JournalJournal of the American Society of Nephrology
Volume10
Issue number9
Publication statusPublished - Sep 1999

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Arachidonate 5-Lipoxygenase
Leukotriene B4
Renal Dialysis
Vitamin E
Cell Membrane
Membranes
Kidney Diseases
Lipid Bilayers
Enzyme Inhibitors
Polymethyl Methacrylate
Membrane Lipids
Hydrogen Peroxide
Lipid Peroxidation
Inhibitory Concentration 50
Blood Cells
Healthy Volunteers
Up-Regulation
Antioxidants
Enzymes
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Maccarrone, M., Taccone-Gallucci, M., Meloni, C., Cococcetta, N., Di Villahermosa, S. M., Casciani, C. U., & Finazzi-Agrò, A. (1999). Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients. Journal of the American Society of Nephrology, 10(9), 1991-1996.

Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients. / Maccarrone, Mauro; Taccone-Gallucci, Massimo; Meloni, Carlo; Cococcetta, Nella; Di Villahermosa, Simone Manca; Casciani, Carlo U.; Finazzi-Agrò, Alessandro.

In: Journal of the American Society of Nephrology, Vol. 10, No. 9, 09.1999, p. 1991-1996.

Research output: Contribution to journalArticle

Maccarrone, M, Taccone-Gallucci, M, Meloni, C, Cococcetta, N, Di Villahermosa, SM, Casciani, CU & Finazzi-Agrò, A 1999, 'Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients', Journal of the American Society of Nephrology, vol. 10, no. 9, pp. 1991-1996.
Maccarrone M, Taccone-Gallucci M, Meloni C, Cococcetta N, Di Villahermosa SM, Casciani CU et al. Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients. Journal of the American Society of Nephrology. 1999 Sep;10(9):1991-1996.
Maccarrone, Mauro ; Taccone-Gallucci, Massimo ; Meloni, Carlo ; Cococcetta, Nella ; Di Villahermosa, Simone Manca ; Casciani, Carlo U. ; Finazzi-Agrò, Alessandro. / Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients. In: Journal of the American Society of Nephrology. 1999 ; Vol. 10, No. 9. pp. 1991-1996.
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