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 similar in many respects to human minimal change nephropathy. The exact aetiologies of both the human and the experimental syndromes are unknown, and are probably multifactorial. However, among the observed consequences in humans and rats is increased plasma protein excretion in urine, beginning in the latter typically 3-6 days after PAN administration. In view of this, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) has been used to profile urinary proteins during PAN-induced nephrotoxicity and subsequent recovery 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 changes in the relative concentrations of a number of metabolites. The proteomic approach, in conjunction with these other techniques, has the potential to provide significantly more mechanistic information than is provided readily by traditional clinical chemistry.
Cutler
P
P
Department of Analytical Sciences, Smith Kline Beecham Pharmaceuticals, Harlow, UK. paul_cutler-1@sbphrd.com
Bell
D J
DJ
Birrell
H C
HC
Connelly
J C
JC
Connor
S C
SC
Holmes
E
E
Mitchell
B C
BC
Monté
S Y
SY
Neville
B A
BA
Pickford
R
R
Polley
S
S
Schneider
K
K
Skehel
J M
JM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D020543:Proteome; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D020543:Proteome; D011692:Puromycin Aminonucleoside