http://www.kidney-international.org & 2009 International Society of Nephrology
original article
Accumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NADPH-dependent mechanisms
Li Li Zhou1, Fan Fan Hou1, Guo Bao Wang1, Fang Yang1, Di Xie1, Yong Ping Wang1 and Jian Wei Tian1
1
Division of Nephrology, Nanfang Hospital, Southern Medical University and Key Lab for Organ Failure Research, Ministry of Education, Guangzhou, P.R. China
The accumulation of plasma advanced oxidation protein products (AOPPs) is prevalent in diverse disorders such as diabetes, metabolic syndromes, and chronic kidney disease. To study whether accumulated AOPPs have an important role in the progression of proteinuria and glomerulosclerosis, we chronically treated normal Sprague–Dawley rats with AOPP-modified rat serum albumin. Podocyte apoptosis was significantly increased coincident with the onset of albuminuria and preceded significant losses of glomerular podocytes. Increasing the amount of AOPPs in the media of conditionally immortalized podocytes rapidly triggered the production of intracellular superoxide by activation of NADPH oxidase and this, in turn, led to an upregulation of p53, Bax, caspase 3 activity, and apoptosis. Chronic inhibition of NADPH oxidase by apocynin prevented podocyte apoptosis, ameliorated podocyte depletion, and decreased albuminuria in AOPP-challenged rats. Our study demonstrates that accumulation of AOPPs promotes NADPH oxidase–dependent podocyte depletion by a p53-Bax apoptotic pathway both in vivo and in vitro.
Kidney International advance online publication, 2 September 2009; doi:10.1038/ki.2009.322 KEYWORDS: AOPPs; NADPH oxidase; podocyte apoptosis; podocyte depletion
Correspondence: Fan Fan Hou, Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, P.R. China. E-mail: ffhou@public.guangzhou.gd.cn Received 26 February 2009; revised 14 June 2009; accepted 7 July 2009

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