Abstract
Accumulation of plasma advanced oxidation protein products (AOPPs) promotes progression of proteinuria and glomerulosclerosis. To investigate the molecular basis of AOPPs-induced proteinuria, normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin. The expression of glomerular podocyte slit diaphragm (PSD)-associated proteins, nephrin and podocin, was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs. Chronic inhibition of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats. This suggested that accumulation of AOPPs promotes proteinuria, possibly via down-regulating the expression of PSD-associated proteins.
Similar content being viewed by others
References
de Zeeuw D, Remuzzi G, Parving H H, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAAL. Kidney Int, 2004, 65: 2309–2320, 10.1111/j.1523-1755.2004.00653.x, 15149345
Huby A C, Rastaldi M P, Caron K, et al. Restoration of podocyte structure and improvement of chronic renal disease in transgenic mice overexpressing renin. PLoS One, 2009, 4: e6721, 10.1371/journal.pone.0006721, 19696925
Xing Y, Ding J, Fan Q, et al. Diversities of podocyte molecular changes induced by different antiproteinuria drugs. Exp Biol Med, 2006, 231: 585–593, 1:CAS:528:DC%2BD28XktlCqsLw%3D
Mao J, Zhang Y, Du L, et al. Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy. Pediatr Nephrol, 2006, 21: 1666–1675, 10.1007/s00467-006-0218-z, 16941146
Li H Y, Hou F F, Zhang X, et al. Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney model. J Am Soc Nephrol, 2007, 18: 528–538, 10.1681/ASN.2006070781, 1:CAS:528:DC%2BD2sXit12ju7s%3D, 17202414
Shi X Y, Hou F F, Niu H X, et al. Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase. Endocrinology, 2008, 149: 1829–1839, 10.1210/en.2007-1544, 1:CAS:528:DC%2BD1cXktVeqsL8%3D, 18174276
Scamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, et al. Early prediction of IgA nephropathy progression: Proteinuria and AOPP are strong prognostic markers. Kidney Int, 2004, 66: 1606–1612, 10.1111/j.1523-1755.2004.00926.x
Huber T B, Benzing T. The slit diaphragm: A signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens, 2005, 14: 211–216, 10.1097/01.mnh.0000165885.85803.a8, 15821412
Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-delta delta C(T)) method. Methods, 2001, 25: 402–408, 10.1006/meth.2001.1262, 1:CAS:528:DC%2BD38XhtFelt7s%3D, 11846609
Saleem M A, O’Hare M J, Reiser J, et al. A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol, 2002, 13: 630–638, 1:CAS:528:DC%2BD38Xit1Wrt74%3D, 11856766
Bass D A, Parce J W, Dechatelet L R, et al. Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J Immunol, 1983, 130: 1910–1917, 1:CAS:528:DyaL3sXhslOgu78%3D, 6833755
Wei X F, Zhou Q G, Hou F F, et al. Advanced oxidation protein products induce mesangial cells perturbation through PKC-dependent activation of NADPH oxidase. Am J Physiol Renal Physiol, 2009, 296: F427–F437, 10.1152/ajprenal.90536.2008, 1:CAS:528:DC%2BD1MXitVeju70%3D, 19019916
Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res, 2002, 51: 597–604, 1:CAS:528:DC%2BD3sXhs1yrtLo%3D, 12511184
Kawachi H, Koike H, Kurihara H, et al. Cloning of rat nephrin: Expression in developing glomeruli and in proteinuric states. Kidney Int, 2000, 57: 1949–1961, 10.1046/j.1523-1755.2000.00044.x, 1:CAS:528:DC%2BD3cXjsFChsrk%3D, 10792613
Reiser J, Kriz W, Kretzler M, et al. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol, 2000, 11: 1–8, 1:STN:280:DC%2BD3c%2FotlWhtg%3D%3D, 10616834
Ruotsalainen V, Ljungberg P, Wartiovaara J, et al. Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc Natl Acad Sci USA, 1999, 96: 7962–7967, 10.1073/pnas.96.14.7962, 1:CAS:528:DyaK1MXltVOkurk%3D, 10393930
Saleem M A, Ni L, Witherden I, et al. Co-localization of nephrin, podocin, and the actin cytoskeleton: Evidence for a role in podocyte foot process formation. Am J Pathol, 2002, 1161: 1459–1466, 1:CAS:528:DC%2BD38Xotl2jtrs%3D, 12368218
Susztak k, Raff A C, Schiffer M, et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes, 2006, 55: 225–233, 10.2337/diabetes.55.01.06.db05-0894, 1:CAS:528:DC%2BD28XlvVSktQ%3D%3D, 16380497
Nistala R, Whaley-Connell A, Sowers J R. Redox control of renal function and hypertension. Antioxid Redox Signal, 2008, 10: 2047–2089, 10.1089/ars.2008.2034, 1:CAS:528:DC%2BD1cXhtFKlsL%2FP, 18821850
Koshikawa M, Mukoyama M, Mori K, et al. Role of p38 mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome. J Am Soc Nephrol, 2005, 16: 2690–2701, 10.1681/ASN.2004121084, 1:CAS:528:DC%2BD2MXhtFeisLrK, 15987752
Lim A K, Nikolic-Paterson D J, Ma F Y, et al. Role of MKK3-p38 MAPK signalling in the development of type 2 diabetes and renal injury in obese db/db mice. Diabetologia, 2009, 52: 347–358, 10.1007/s00125-008-1215-5, 1:CAS:528:DC%2BD1MXjvFGjuw%3D%3D, 19066844
Huber T B, Benzing T. The slit diaphragm:a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens, 2005, 14: 211–216, 10.1097/01.mnh.0000165885.85803.a8, 15821412
Kalousová M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res, 2002, 51: 597–604, 12511184
Atabek M E, Keskin M, Yazici C, et al. Protein oxidation in obesity and insulin resistance. Eur J Pediatr, 2006, 165: 753–756, 10.1007/s00431-006-0165-5, 1:CAS:528:DC%2BD28XpvVarurw%3D, 16710733
Scamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, et al. Early prediction of IgA nephropathy progression: Proteinuria and AOPP are strong prognostic markers. Kidney Int, 2004, 66: 1606–1612, 10.1111/j.1523-1755.2004.00926.x
Roselli S, Heidet L, Sich M, et al. Early glomerular filtration defect and severe renal disease in podocin-deficient mice. Mol Cell Biol, 2004, 24: 550–560, 10.1128/MCB.24.2.550-560.2004, 1:CAS:528:DC%2BD2cXktVymsQ%3D%3D, 14701729
Mollet G, Ratelade J, Boyer O, et al. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome. J Am Soc Nephrol, 2009, 20: 2181–2189, 10.1681/ASN.2009040379, 1:CAS:528:DC%2BD1MXhtlSrsbfN, 19713307
Li J J, Kwak S J, Jung D S, et al. Podocyte biology in diabetic nephropathy. Kidney Int, 2007, 72: S36–S42, 10.1038/sj.ki.5002384
Guo Z J, Niu H X, Hou F F, et al. Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. Antioxid Redox Signal, 2008, 10: 1699–1712, 10.1089/ars.2007.1999, 1:CAS:528:DC%2BD1cXpvFGru70%3D, 18576917
Author information
Authors and Affiliations
Corresponding author
Additional information
Contributed equally to this work
Rights and permissions
About this article
Cite this article
Yang, L., Liang, M., Zhou, Q. et al. Advanced oxidation protein products decrease expression of nephrin and podocin in podocytes via ROS-dependent activation of p38 MAPK. Sci. China Life Sci. 53, 68–77 (2010). https://doi.org/10.1007/s11427-010-0014-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-010-0014-7