Assessment of the effect of 24-hour aldosterone administration on protein abundance in fluorescence-sorted mouse distal renal tubules by mass spectrometry

Nephron Physiol. 2012;121(3-4):p9-15. doi: 10.1159/000346832. Epub 2013 Feb 14.

Abstract

Background/aims: Aldosterone exerts multiple long-term effects on the distal renal tubules. The aim of this study was to establish a method for identifying proteins in these tubules that change in abundance by only 24-hour aldosterone administration.

Methods: Mice endogenously expressing green fluorescent protein (eGFP) in the connecting tubule and cortical collecting ducts were treated with a subcutaneous injection of 2.0 mg/kg aldosterone or vehicle (n = 5), and sacrificed 24 h later. Suspensions of single cells were obtained enzymatically, and eGFP-positive cells were isolated by fluorescence-activated cell sorting (FACS). Samples of 100 µg of proteins were digested with trypsin and labeled with 8-plex isobaric tags for relative and absolute quantitation reagents and processed for liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: FACS yielded 1.4 million cells per mouse. The LC-MS/MS spectra were matched to peptides by the SEQUEST search algorithm, which identified 3,002 peptides corresponding to 506 unique proteins, of which 20 significantly changed abundance 24 h after aldosterone injection.

Conclusion: We find the method suitable and useful for studying hormonal effects on protein abundance in distal tubular segments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / administration & dosage*
  • Aldosterone / blood
  • Animals
  • Cell Separation / methods*
  • Chromatography, Liquid
  • Flow Cytometry*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Injections, Subcutaneous
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism
  • Kidney Tubules, Distal / drug effects*
  • Kidney Tubules, Distal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Mapping
  • Proteins / metabolism*
  • Proteomics / methods
  • Reproducibility of Results
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Aldosterone