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| Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients |
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| Author(s): Maccarrone M, Taccone-Gallucci M, Meloni C, Cococcetta N, Di Villahermosa SM, Casciani CU, Finazzi-Agro A |
| Source: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Volume: 10 Issue: 9 Pages: 1991-1996 Published: SEP 1999 |
| Times Cited: 20 References: 30 |
| 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 A(234/205) ratio) of membrane lipids was 3.2-fold higher in hemodialysis patients than in healthy control subjects, and also the level of leukotriene B-4 was significantly increased (up to 1.7-fold over control). Both membrane peroxidation and release of leukotriene B-4 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 B-4 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 mu M), further characterized as noncompetitive (Ki = 30 +/- 3 mu M). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Finazzi-Agro, A (reprint author), Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Via Tor Vergata 135, I-00133 Rome, Italy |
Addresses:
1. Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
2. Univ Roma Tor Vergata, Chair Nephrol, I-00133 Rome, Italy
3. Univ Roma Tor Vergata, Chair Surg, I-00133 Rome, Italy
4. CNR, Tissue Typing Inst, Laquila, Italy |
| Publisher: LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA |
| Subject Category: Urology & Nephrology |
| IDS Number: 229UB |
| ISSN: 1046-6673 |
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