5-Lipoxygenase-mediated mitochondrial damage and apoptosis of mononuclear cells in ESRD patients

Mauro Maccarrone, Massimo Taccone-Gallucci, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticle

Abstract

Background. 5-Lipoxygenase activity is enhanced in peripheral blood mononuclear cells (PBMC) from end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD), leading to lipoperoxidation and reactive oxygen species formation. These effects are prevented by vitamin E, which inhibits 5-lipoxygenase activity. The present study was designed to test the possibility that 5-lipoxygenase activation might cause mitochondrial damage and cytochrome c release, ultimately leading PBMC to apoptosis. Methods. Apoptosis, mitochondrial uncoupling, and cytochrome c release were investigated in PBMC from 16 healthy volunteers and 16 ESRD patients on maintenance HD with cuprammonium rayon (CL-S) membranes in a two-step crossover study: after a four-week treatment with vitamin E-coated cuprammonium rayon (CL-E) membranes, and again after a four-week treatment with oral vitamin E. Results. Compared to healthy controls, PBMC from ESRD patients showed a ∼threefold increase in mitochondrial uncoupling and cytochrome c release (within 4 and 8 hours, respectively), followed by a ∼threefold increase in apoptotic body formation (within 48 hours). Regardless of the administration route, vitamin E reduced mitochondrial uncoupling, cytochrome c release and apoptosis of mononuclear cells, as did the 5-lipoxygenase inhibitor eicosatetraynoic acid. Conversely, the cyclooxygenase inhibitor indomethacin was ineffective. Conclusions. Reported data suggest that the 5-lipoxygenase branch of the arachidonate cascade is only responsible for mitochondrial disruption and apoptosis of PBMC of ESRD patients, and that vitamin E may be helpful in the control of oxidative stress-related disease in these subjects, independent of the administration route.

Original languageEnglish
JournalKidney international. Supplement
Volume63
Issue number84
Publication statusPublished - May 2003

Keywords

  • 5-Lipoxygenase
  • Apoptosis
  • Cytochrome c
  • Hemodialysis
  • Mitochondria
  • Peripheral blood mononuclear cells
  • Vitamin E

ASJC Scopus subject areas

  • Nephrology

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