This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shi, X. Y. Articles by Zhang, X. Search for Related Content PubMed PubMed Citation Articles by Shi, X. Y. Articles by Zhang, X. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Diabetic Kidney Problems

Advanced Oxidation Protein Products Promote Inflammation in Diabetic Kidney through Activation of Renal Nicotinamide Adenine Dinucleotide Phosphate Oxidase

Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China

Address all correspondence and requests for reprints to: Dr. Fan Fan Hou, Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China. E-mail: ffhou{at}public.guangzhou.gd.cn.

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-β1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47^phox and gp91^phox. All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.

This article has been cited by other articles:

				L. J. He, M. Liang, F. F. Hou, Z. J. Guo, D. Xie, and X. Zhang Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action J. Endocrinol., March 1, 2009; 200(3): 347 - 355. [Abstract] [Full Text] [PDF]

				X. F. Wei, Q. G. Zhou, F. F. Hou, B. Y. Liu, and M. Liang Advanced oxidation protein products induce mesangial cell perturbation through PKC-dependent activation of NADPH oxidase Am J Physiol Renal Physiol, February 1, 2009; 296(2): F427 - F437. [Abstract] [Full Text] [PDF]

				H. L. Liang, G. Hilton, J. Mortensen, K. Regner, C. P. Johnson, and V. Nilakantan MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis following renal ischemia-reperfusion Am J Physiol Renal Physiol, February 1, 2009; 296(2): F266 - F276. [Abstract] [Full Text] [PDF]