Urinary protein profiling with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in etB receptor-deficient rats1

Jens Raila, Philipp Kalk, Thiemo Pfab, Christa Thöne-Reineke, Michael Godes, Masashi Yanagisawa, Florian J. Schweigert, Berthold Hocher

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)566-570
Number of pages5
JournalCanadian Journal of Physiology and Pharmacology
Volume86
Issue number8
DOIs
StatePublished - Aug 1 2008

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Keywords

  • Albuminuria
  • Biomarker discovery
  • Endothelin
  • Endothelin B receptor-deficient rats
  • Kidney fibrosis
  • Proteinuria
  • Proteomics
  • SELDI-TOF-mass spectrometry
  • Urinary protein pattern
  • Urine

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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