title: Urinary protein profiling with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in ETB receptor-deficient rats.
abstract: The pathways leading to salt-sensitive hypertension and renal damage in rescued ETB receptor-deficient (ETBRd) rats are still unknown. The objective of the study was therefore to identify modifications of urinary peptide and protein expression in ETBRd rats (n = 9) and wild-type controls (n = 6) using SDS - polyacrylamide gel electrophoresis (SDS-PAGE) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. Glomerular filtration rate, glomerulosclerosis, and tubulointerstitial fibrosis did not differ between the groups. ETBRd rats showed slightly higher blood pressure (p < 0.001), media/lumen ratio of intrarenal arteries (p < 0.01), and albuminuria (p < 0.01). SDS-PAGE confirmed albuminuria, but showed no differences in the urinary excretion of low molecular weight proteins (<60 kDa). SELDI-TOF-MS profiling revealed 9 proteomic features at molecular masses (Da) of 2720, 2980, 3130, 3345, 6466, 6682, 8550, 18 729, and 37 492, which were significantly elevated (p < 0.02) in urine of ETBRd rats. The results demonstrate that, independent of structural changes in the kidneys, ETB-receptor deficiency causes specific differences in urinary peptide and protein excretion. SELDI-TOF-MS may be a valuable tool for the characterization of urinary biomarkers helping to uncover the mechanism of ETBR action in the kidney.
authors.affiliation: Institute of Nutritional Science, Department of Physiology and Pathophysiology of Nutrition, University of Potsdam, Potsdam, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Raila
authors.forename: Philipp
authors.initials: P
authors.lastname: Kalk
authors.forename: Thiemo
authors.initials: T
authors.lastname: Pfab
authors.forename: Christa
authors.initials: C
authors.lastname: Thöne-Reineke
authors.forename: Michael
authors.initials: M
authors.lastname: Godes
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Schweigert
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher