An integrated proteomic approach to studying glomerular nephrotoxicity

A single dose of puromycin aminonucleoside (PAN) given parenterally to rats induces ultrastructural glomerular changes and a nephrotic syndrome simila r in many respects to human minimal change nephropathy. The exact aetiologi es of both the human and the experimental syndromes are unknown, and are pr obably multifactorial. However, among the observed consequences in humans a nd rats is increased plasma protein excretion in urine, beginning in the la tter typically 3-6 days after PAN administration. In view of this, two-dime nsional polyacrylamide gel electrophoresis (2-D PAGE) has been used to prof ile urinary proteins during PAN-induced nephrotoxicity and subsequent recov ery in the rat. In addition, urinary high performance liquid chromatography (HPLC) profiles and high resolution proton nuclear magnetic resonance (NMR ) spectroscopy has been utilised to simultaneously detect toxin-induced cha nges in the relative concentrations of a number of metabolites. The proteom ic approach, in conjunction with these other techniques, has the potential to provide significantly more mechanistic information than is provided read ily by traditional clinical chemistry.