Nitrosative and oxidative stress induced heme oxygenase-1 accumulation in rat mesangial cells. 1998

K Sandau, and J Pfeilschifter, and B Brüne
Department of Medicine IV, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.

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.

UI MeSH Term Description Entries
D009285 Naphthoquinones Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. Naphthalenediones,Naphthazarins,Naphthoquinone
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009603 Nitroso Compounds Organic compounds containing the nitroso (-N Compounds, Nitroso
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D005920 Glomerular Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX. Mesangium, Glomerular,Mesangial Extracellular Matrix,Extracellular Matrices, Mesangial,Extracellular Matrix, Mesangial,Glomerular Mesangiums,Matrices, Mesangial Extracellular,Matrix, Mesangial Extracellular,Mesangial Extracellular Matrices,Mesangiums, Glomerular
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006419 Heme Oxygenase (Decyclizing) A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation

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