Advanced oxidation protein products decrease expression of nephrin and podocin in podocytes via ROS-dependent activation of p38 MAPK.
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.
Yang
Li
L
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Liang
Min
M
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Zhou
QiuGen
Q
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Xie
Di
D
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Lou
AiJu
A
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Zhang
Xun
X
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Hou
FanFan
F
Key Laboratory for organ failure research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. ffhou@public.guangzhou.gd.cn.
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D011506:Proteins; D017382:Reactive Oxygen Species; D012709:Serum Albumin; C113267:nephrin; D048051:p38 Mitogen-Activated Protein Kinases