Kidney international, 2012-10, Vol.82 (7), p.759-770
2012
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Details
- Autor(en) / Beteiligte
- Titel
- The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis
- Ist Teil von
- Kidney international, 2012-10, Vol.82 (7), p.759-770
- Ort / Verlag
- Basingstoke: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- The accumulation of plasma advanced oxidation protein products (AOPPs) is prevalent in chronic kidney disease. We previously showed that accumulation of AOPPs resulted in podocyte apoptosis and their deletion by a cascade of signaling events coupled with intracellular oxidative stress. The transmembrane receptor that specifically transmits the AOPPs' signals to elicit cellular activity, however, remains unknown. Using co-immunoprecipitation and immunofluorescence, we found that AOPPs colocalized and interacted with the receptor of advanced glycation end products (RAGE) on podocytes. Blocking RAGE by anti-RAGE immunoglobulin G or its silencing by siRNA significantly protected podocytes from AOPPs-induced apoptosis both in vitro and in vivo and ameliorated albuminuria in AOPPs-challenged mice. AOPPs-induced activation of nicotinamide adenine dinucleotide phosphate oxidase and the excessive generation of intracellular superoxide were largely inhibited by anti-RAGE immunoglobulin G or RAGE siRNA. Moreover, blockade of RAGE decreased the activation of the p53/Bax/caspase-dependent proapoptotic pathway induced by AOPPs. Thus, AOPPs interact with RAGE to induce podocyte apoptosis and this, in part, may contribute to the progression of chronic kidney disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0085-2538eISSN: 1523-1755DOI: 10.1038/ki.2012.184Titel-ID: cdi_proquest_miscellaneous_1151032480
- Format
- –
- Schlagworte
- Advanced Oxidation Protein Products - administration & dosage, Advanced Oxidation Protein Products - metabolism, Albuminuria - metabolism, Albuminuria - prevention & control, Animals, AOPPs, Apoptosis, bcl-2-Associated X Protein - metabolism, Biological and medical sciences, Caspase 3 - metabolism, Cell Line, Disease Progression, Enzyme Activation, Fluorescent Antibody Technique, Immunoglobulin G - administration & dosage, Immunoprecipitation, Injections, Intravenous, Male, Medical sciences, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NADPH Oxidases - metabolism, Nephrology. Urinary tract diseases, podocyte, Podocytes - immunology, Podocytes - metabolism, Podocytes - pathology, RAGE, Receptor for Advanced Glycation End Products, Receptors, Immunologic - genetics, Receptors, Immunologic - immunology, Receptors, Immunologic - metabolism, Renal Insufficiency, Chronic - immunology, Renal Insufficiency, Chronic - metabolism, Renal Insufficiency, Chronic - pathology, Renal Insufficiency, Chronic - prevention & control, RNA Interference, Signal Transduction, Superoxides - metabolism, Time Factors, Transfection, Tumor Suppressor Protein p53 - metabolism