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. 2012 Oct;82(7):759-70.
doi: 10.1038/ki.2012.184. Epub 2012 May 23.

The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis

Li Li Zhou  1 , Wei Cao, Chao Xie, Jianwei Tian, Zhanmei Zhou, Qiugen Zhou, Ping Zhu, Aiqing Li, Youhua Liu, Toshio Miyata, Fan Fan Hou, Jing Nie
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Free article

The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis

Li Li Zhou et al. Kidney Int. 2012 Oct.
Free article

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.

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