Nitrosative and oxidative stress induced heme oxygenase-1 accumulation in rat mesangial cells.
The formation of nitric oxide (NO.) and superoxide (O2-) promotes rat mesangial cell death. Apoptotic death is characterized by DNA fragmentation, caspase-3 activation and concomitant poly(ADPribose) polymerase cleavage, as well as accumulation of the tumor suppressor protein p53. In close association with apoptotic parameters we noticed upregulation of heme oxygenase by the NO donor S-nitrosoglutathione (GSNO) and the redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in a time- and concentration-dependent manner. In response to the NO. donor, heme oxygenase-1 expression was more easily obtained than initiation of apoptosis. Radical (NO./O2-) cogeneration abrogated DNA fragmentation, suppressed caspase activation and lowered p53 accumulation, thereby promoting cell survival of mesangial cells. In contrast, heme oxygenase-1 expression remained elevated under conditions of GSNO/DMNQ coadministration. Conclusively, heme oxygenase-1 is a stress marker for both nitrosative and oxidative stress. Accumulation of heme oxygenase-1 is found under conditions of both, apoptotic cell death and cell survival, thereby questioning a specific cytoprotective role of heme oxygenase-1 under conditions of NO. and/or O2- formation in rat mesangial cells.
Sandau
K
K
Department of Medicine IV, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
Pfeilschifter
J
J
Brüne
B
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004790:Enzyme Induction / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D009285:Naphthoquinones / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D026422:S-Nitrosoglutathione; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D009285:Naphthoquinones; D018696:Neuroprotective Agents; D009603:Nitroso Compounds; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C063002:2,3-dimethoxy-1,4-naphthoquinone; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione