+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Redox Signaling in Mesangial Cells

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references 8

          • Record: found
          • Abstract: found
          • Article: not found

          Identification of renox, an NAD(P)H oxidase in kidney.

          Oxygen sensing is essential for homeostasis in all aerobic organisms, but its mechanism is poorly understood. Data suggest that a phagocytic-like NAD(P)H oxidase producing reactive oxygen species serves as a primary sensor for oxygen. We have characterized a source of superoxide anions in the kidney that we refer to as a renal NAD(P)H oxidase or Renox. Renox is homologous to gp91(phox) (91-kDa subunit of the phagocyte oxidase), the electron-transporting subunit of phagocytic NADPH oxidase, and contains all of the structural motifs considered essential for binding of heme, flavin, and nucleotide. In situ RNA hybridization revealed that renox is highly expressed at the site of erythropoietin production in the renal cortex, showing the greatest accumulation of renox mRNA in proximal convoluted tubule epithelial cells. NIH 3T3 fibroblasts overexpressing transfected Renox show increased production of superoxide and develop signs of cellular senescence. Our data suggest that Renox, as a renal source of reactive oxygen species, is a likely candidate for the oxygen sensor function regulating oxygen-dependent gene expression and may also have a role in the development of inflammatory processes in the kidney.
            • Record: found
            • Abstract: found
            • Article: not found

            Redox signaling and the emerging therapeutic potential of thiol antioxidants.

             Chandan Sen (1998)
            Oxidation-reduction (redox) based regulation of signal transduction and gene expression is emerging as a fundamental regulatory mechanism in cell biology. Electron flow through side chain functional CH2-SH groups of conserved cysteinyl residues in proteins account for their redox-sensing properties. Because in most intracellular proteins thiol groups are strongly "buffered" against oxidation by the highly reduced environment inside the cell, only accessible protein thiol groups with high thiol-disulfide oxidation potentials are likely to be redox sensitive. The list of redox-sensitive signal transduction pathways is steadily growing, and current information suggests that manipulation of the cell redox state may prove to be an important strategy for the management of AIDS and some forms of cancer. The endogenous thioredoxin and glutathione systems are of central importance in redox signaling. Among the thiol agents tested for their efficacy to modulate cellular redox status, N-acetyl-L-cysteine (NAC) and alpha-lipoic acid hold promise for clinical use. A unique advantage of lipoate is that it is able to utilize cellular reducing equivalents, and thus it harnesses the metabolic power of the cell to continuously regenerate its reductive vicinal dithiol form. Because lipoate can be readily recycled in the cell, it has an advantage over N-acetyl-L-cysteine on a concentration:effect basis. Our current knowledge of redox regulated signal transduction has led to the unfolding of the remarkable therapeutic potential of cellular thiol modulating agents.
              • Record: found
              • Abstract: found
              • Article: not found

              Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells.

               S Gauer,  K Beck,  T Beeg (1999)
              Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells. High-output levels of nitric oxide (NO) are produced by rat mesangial cells (MCs) in response to proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) by the inducible isoform of NO synthase (iNOS). We tested modulatory effects of NO on the expression and activities of matrix metalloproteinases-9 and -2 (MMP-9 and MMP-2), respectively. Temporal and spatial expression of these MMPs and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), seems to be critical in the extensive extracellular matrix (ECM) remodeling that accompanies sclerotic processes of the mesangium. Methods and Results. Using the NO donors S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETA-NONOate, we found strong inhibitory effects of NO mainly on the IL-1beta-induced MMP-9 mRNA levels. NO on its own had only weak effects on the expression of MMP-9 and MMP-2. The addition of the NOS inhibitor NG-monomethyl L-arginine (L-NMMA) dose dependently increased steady-state mRNA levels of cytokine-induced MMP-9, suggesting that endogenously produced NO exerts tonic inhibition of MMP-9 expression. MMP-9 activity in conditioned media from MCs costimulated with IL-1beta and NO donor contained less gelatinolytic activity than media of cells treated with IL-1beta alone. Exogenously added NO did not alter gelatinolytic activity of MMP-9 in cell-free zymographs. The expression levels of TIMP-1 were affected by NO similarly to the expression of MMP-9. We conclude that NO modulates cytokine-mediated expression of MMP-9 and TIMP-1 in rat MCs in culture. Our results provide evidence that NO-mediated attenuation of MMP-9 gelatinolytic activity is primarily due to a reduced expression of MMP-9 mRNA, and not the result of direct inhibition of enzymatic activity.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                January 2003
                17 November 2004
                : 93
                : 1
                : e23-e26
                Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, FrankfurtamMain, Deutschland
                66652 Nephron Exp Nephrol 2003;93:e23–e26
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 16, Pages: 1
                Self URI (application/pdf):


                Comment on this article