Induction of heme oxygenase-1 mediates cell death in a leukemia cell line.

BATTLE A; NORIEGA G; MARTIN G; CRICCO G; RIVERA E; TOMARO ML

Washington DC, USA

Congreso; Experimental Biology 2004.; 2004

American Societies for Experimental Biology.

We have previously demonstrated that bilirubin is highly effective in preventing the oxidative cell damage induced by different compounds in rat liver. In this study we have evaluated the effect of heme oxygenase-1 (HO-1) on cell death in a myeloid cell line. Upon exposure of U937 cells to 200 mM H2O2 during 24 h, cell viability was 58%reduced, assessed by the acridin orange and ethidium bromide assay, the thiobarbituric acid reactive substances (TBARS) were 434% enhanced and the antioxidant enzyme activities, catalase (CAT) and glutathione-peroxidase (GSH-PX) were 35% and 32% inhibited respectively. Bilirubin (10 mM) entirely prevented the effects caused by H2O2. A 3.5 fold induction of HO-1 activity was observed in the H2O2 treated cells. Inhibition of HO-1 by Zn protoporphyrin IX (ZnPPIX) prevented cell death and enhanced CAT and GSH-Px activities (19% and 42%, respectively). These results prompted us to evaluate ferritin levels. Surprisingly, there was a 72% diminution in the amount of this protein when HO-1 was induced. Ferritin synthesis causes a reduction of free iron in the cell and thereby attenuates oxidative susceptibility. This work clearly demonstrates that overexpression of HO-1 aggravates oxidative stress damage, because iron-mediated oxidant propagation overwhelms the antioxidant capacity of HO-1.   poster