Heme oxygenase does not protect human cells against oxidant stress
- PMID: 8144999
Heme oxygenase does not protect human cells against oxidant stress
Abstract
The induction of heme oxygenase in cells under conditions of oxidative stress has been hypothesized to represent a cellular antioxidant defense mechanism. The objectives of this study were to characterize the induction of heme oxygenase by the oxidant stress-inducing quinone agent menadione (2-methyl-1,4-naphthoquinone) and to elucidate the roles of basal and induced heme oxygenase enzyme activities in menadione-induced DNA damage and growth inhibition in human MCF-7 cells. Time- and dose-dependent inductions of heme oxygenase messenger RNA and enzyme activity in menadione-treated MCF-7 cells were demonstrated. Intracellular and extracellular bilirubin concentrations were less than 100 nmol/L and were not altered when heme oxygenase was induced. The roles of the basal and induced heme oxygenase enzyme activities in menadione-mediated DNA damage were evaluated by means of the heme oxygenase competitive inhibitor tin protoporphyrin. Inhibition of the basal heme oxygenase enzyme activity by tin protoporphyrin resulted in a decrease in the number of menadione-induced DNA breaks and an attenuation of the cellular growth inhibition caused by menadione. Induced heme oxygenase did not protect MCF-7 cells from menadione-induced DNA breaks. Basal heme oxygenase enzyme activities in two cloned menadione-resistant cell lines were significantly less than that measured in a menadione-sensitive parental MCF-7 cell line. Collectively, these data do not support a protective role for basal or induced heme oxygenase enzyme activities against oxidant stress-related DNA strand breakage or cytotoxic effects engendered by menadione in human cells.
Comment in
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The functional significance of induction of heme oxygenase by oxidant stress.J Lab Clin Med. 1994 Apr;123(4):461-3. J Lab Clin Med. 1994. PMID: 8144993 No abstract available.
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