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

Area of Science:

• Nephrology
• Molecular Biology
• Biochemistry

Background:

• Plasma advanced oxidation protein products (AOPPs) are implicated in the progression of proteinuria and glomerulosclerosis.
• Understanding the molecular mechanisms underlying AOPP-induced kidney damage is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the molecular basis of how advanced oxidation protein products (AOPPs) induce proteinuria.
• To examine the effect of AOPPs on glomerular podocyte slit diaphragm (PSD)-associated proteins.

Main Methods:

• Normal Sprague-Dawley rats were administered AOPPs-modified rat serum albumin.
• Expression levels of nephrin and podocin were assessed.
• The impact of NADPH oxidase inhibition with apocynin was evaluated.

Main Results:

• AOPP administration led to a significant decrease in nephrin and podocin expression, correlating with the onset of albuminuria.
• Chronic inhibition of NADPH oxidase using apocynin prevented the down-regulation of nephrin and podocin.
• Apocynin treatment also attenuated albuminuria in rats challenged with AOPPs.

Conclusions:

• Accumulation of AOPPs promotes proteinuria by down-regulating the expression of glomerular podocyte slit diaphragm (PSD)-associated proteins, nephrin and podocin.
• NADPH oxidase appears to play a key role in the pathogenesis of AOPP-induced proteinuria.