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The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis.
- Source :
-
Kidney International . Oct2012, Vol. 82 Issue 7, p759-770. 12p. 7 Graphs. - Publication Year :
- 2012
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00852538
- Volume :
- 82
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Kidney International
- Publication Type :
- Academic Journal
- Accession number :
- 79960867
- Full Text :
- https://doi.org/10.1038/ki.2012.184