Heme oxygenase (HO)-1 is a stress-inducible enzyme protecting cells against oxidative stress, and mechanisms have been considered to depend exclusively on its enzyme activity. This study aimed to examine if the protein lacking catalytic activities could also display such resistance against oxidative stress. Stable transfectants of rat wild type HO-1 cDNA (HO-1-U937) and those of its H25A mutant gene (mHO-1-U937) were established using human monoblastic lymphoma cell U937. HO-1-U937 and mHO-1-U937 used in the study exhibited similar levels of the protein expression, while only the former increased enzyme activities. HO-1-and mHO-1 U937 cells became more and less sensitive to H 2 O 2 than mock transfectants, respectively; such distinct susceptibility between the cells was ascribable to differences in the capacity to scavenge H 2 O 2 through catalase and to execute iron-mediated oxidant propagation. On the other hand, both cell lines exhibited greater resistance to tertbutyl hydroperoxide than mock transfectants. The resistance of HO-1-U937 to hydroperoxides appeared to result from antioxidant properties of bilirubin, an HOderived product, while that of mHO-1-U937 was ascribable to increased contents of catalase and glutathione.

Background:Persistent hypoalbuminemia is a predictor of death in long-term maintenance hemodialysis patients, although cardiovascular diseases remain the leading cause of death. A decreased serum antioxidant activity in maintenance hemodialysis patients may contribute to increased oxidative damage, and may be associated with accelerated atherosclerotic changes. Methods:The aim of this study was to examine the redox state of human serum albumin in maintenance hemodialysis patients by high-performance liquid chromatography (HPLC) using a fluorescence detector. Results: HPLC of human serum albumin on a Shodex-Asahipak ES-502N column at pH 4.85 showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are the reduced and oxidized forms of human serum albumin, respectively. The mean ± SD percentage of the HMA fraction of human serum albumin was significantly lower in maintenance hemodialysis patients than in age-matched normal subjects. The percentage of HMA increased 3–5 h after starting the hemodialysis and then decreased to subnormal levels. Conclusion: This suggests that serum albumin may be a major extracellular antioxidant in maintenance hemodialysis patients, and that hemodialysis may rescue serum albumin reduction by inducing intermolecular sulfhydryl-disulfide exchange reaction.

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