Advanced oxidation protein products decrease expression of nephrin and podocin in podocytes via ROS-dependent activation of p38 MAPK

Sci China Life Sci. 2010 Jan;53(1):68-77. doi: 10.1007/s11427-010-0014-7. Epub 2010 Feb 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Oxidation-Reduction
  • Podocytes / cytology
  • Podocytes / drug effects*
  • Podocytes / metabolism
  • Proteins / chemistry
  • Proteinuria / chemically induced
  • Proteinuria / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin / chemistry
  • Serum Albumin / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Proteins
  • Reactive Oxygen Species
  • Serum Albumin
  • nephrin
  • p38 Mitogen-Activated Protein Kinases