Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment.
Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure oxygen under high ambient pressure) indicated clearly increased levels of HO-1 in lymphocytes of volunteers 24 h after HBO treatment (1 h at 1.5 bar). Experiments with the comet assay (alkaline single cell gel electrophoresis) revealed that the same cells were almost completely protected against the induction of DNA damage by a repeated exposure or in vitro treatment with H(2)O(2) 24 h after the first HBO. In order to further investigate the role of HO-1 in HBO-induced adaptive response, we now performed experiments with isolated human lymphocytes exposed to HBO in vitro (2 h at 3 bar). Our results show that also under cell culture conditions, lymphocytes exhibit an adaptive protection similar to that observed in our previous work with healthy human subjects. The time-course of HO-1 induction proceeds in parallel to the development of an adaptive protection against the induction of oxidative DNA damage. A comparable protection was not seen in V79 cells, indicating a specific difference between the two investigated cell systems. Treatment with the specific HO-1 inhibitor tin-mesoporphyrin IX (SnMP) led to a complete abrogation of HBO-induced adaptive protection in human lymphocytes. Our results indicate a functional involvement of HO-1 in the adaptive protection of human lymphocytes against the induction of oxidative DNA damage. The exact mechanism by which HO-1 contributes to an adaptive response remains to be elucidated.
Rothfuss
A
A
Abteilung Humangenetik and Sektion Anästhesiologie und Pathophysiologische Verfahrensentwicklung, Universitätsklinikum Ulm, D-89070 Ulm, Germany.
Radermacher
P
P
Speit
G
G
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006931:Hyperbaric Oxygenation; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D008565:Membrane Proteins; D008665:Metalloporphyrins; D012333:RNA, Messenger; C055421:tin mesoporphyrin; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010100:Oxygen