Investigations on the mechanism of hyperbaric oxygen (HBO)-induced adaptive protection against oxidative stress.
Hyperbaric oxygen (HBO) treatment of cell cultures is a well suited model for studying genetic and cellular consequences of oxidative stress. We have previously shown that exposure of isolated human lymphocytes to HBO induces DNA damage and leads to the development of an adaptive response which protects lymphocytes from oxidative DNA damage induced by a repeated HBO exposure or by treatment with H(2)O(2). Our earlier studies also provided evidence for a functional involvement of the inducible enzyme heme oxygenase-1 (HO-1) in this adaptive protection. In contrast, V79 Chinese hamster cells did neither show a comparable adaptive protection nor an induction of HO-1 after HBO exposure. We now investigated possible mechanism(s) by which HO-1 contributes to an enhanced resistance of lymphocytes against oxidative stress. HO-1 catalyzes the rate-limiting step in heme degradation to form carbon monoxide (CO), biliverdin and free iron. We can now show that supplementation with exogenous CO does not protect V79 cells from HBO-induced oxidative DNA damage suggesting that increased generation of CO cannot account for the observed adaptive protection. On the other hand, HBO-exposed lymphocytes showed a small but reproducible increase in cellular ferritin levels, which might indicate that the underlying protective mechanism is based on an induction of ferritin, which may act antioxidatively by preventing the generation of the DNA-damaging hydroxyl radical via Fenton reaction. Our results further show that isolated lymphocytes also induce HO-1 and develop an adaptive protection when the first HBO exposure does not induce DNA damage, indicating that DNA damage is not the trigger for the development of the adaptive protection.
Rothfuss
Andreas
A
Universitätsklinikum Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany.
Speit
Günter
G
D000222:Adaptation, Physiological; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D002478:Cells, Cultured; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects; D005293:Ferritins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D006931:Hyperbaric Oxygenation; D008214:Lymphocytes / Q000502:physiology*; D008565:Membrane Proteins; D015162:Micronucleus Tests; D018384:Oxidative Stress
D008565:Membrane Proteins; D002248:Carbon Monoxide; D005293:Ferritins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1