Mesangial cells but not hepatocytes are protected against NO/O(2)(-) cogeneration: mechanistic considerations.
Reactive oxygen and nitrogen species such as superoxide (O(2)(-)) and nitric oxide (NO) are produced under diverse conditions and provoke distinct signaling reactions. The formation of NO has been shown to induce apoptosis and/or necrosis in mesangial cells and to protect other cells such as hepatocytes. Often, NO and O(2)(-) are simultaneously generated, which results in their diffusion-controlled interaction and, thus, redirects the signaling properties of either NO or O(2)(-). This has been proven for mesangial cells, where O(2)(-) formation attenuates NO-initiated apoptosis. As the mechanisms involved remained unclear, we studied the potential impact of the glutathione redox system and compared the results obtained with mesangial cells with those obtained with Hep G2 hepatocytes. In contrast to mesangial cells, Hep G2 cells appeared resistant to NO donors but displayed massive cell destruction following NO/O(2)(-) cogeneration. As a result, we noticed a greater increase in GSSG levels in Hep G2 cells than in mesangial cells. GSH depletion reversed the cell protection in mesangial cells and enhanced the cell damage in Hep G2 cells. NO/O(2)(-)-mediated mesangial protection is associated with an increased glutathione reductase activity and an increase in GSH. In conclusion, NO/O(2)(-) sensitivity is cell type specific and is determined by the glutathione redox system.
Department of Cell Biology, Faculty of Biology, University of Kaiserslautern, Erwin-Schrödinger-Strasse, 67663, Kaiserslautern, Germany.
Vadim V
VV
Sumbayev
Katrin B
KB
Sandau
Bernhard
B
Brüne
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D019803:Glutathione Disulfide / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008967:Molecular Biology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D005980:Glutathione Reductase; D019803:Glutathione Disulfide