Quantitative proteomic analysis of a genetically induced prostate inflammation mouse model via custom 4-plex DiLeu isobaric labeling

Ling Hao, Samuel Thomas, Tyler Greer, Chad M. Vezina, Sagar Bajpai, Arya Ashok, Angelo M. De Marzo, Charles J. Bieberich, Lingjun Li, William A. Ricke

Research output: Contribution to journalArticle

Abstract

Inflammation is involved in many prostate pathologies including infection, benign prostatic hyperplasia, and prostate cancer. Preclinical models are critical to our understanding of disease mechanisms, yet few models are genetically tractable. Here, we present a comparative quantitative proteomic analysis of urine from mice with and without prostate-specific inflammation induced by conditional prostate epithelial IL-1β expression. Relative quantification and sample multiplexing was achieved using custom 4-plex N,N-dimethyl leucine (DiLeu) isobaric tags and nanoflow ultrahigh-performance liquid chromatography coupled to high-resolution tandem mass spectrometry. Each set of 4-plex DiLeu reagents allows four urine samples to be analyzed simultaneously, providing high-throughput and accurate quantification of urinary proteins. Proteins involved in the acute phase response, including haptoglobin, inter-α-trypsin inhibitor, and α1-antitrypsin 1-1, were differentially represented in the urine of mice with prostate inflammation. Mass spectrometry-based quantitative urinary proteomics represents a promising bioanalytical strategy for biomarker discovery and the elucidation of molecular mechanisms in urological research.

Original languageEnglish (US)
Pages (from-to)F1236-F1243
JournalAmerican Journal of Physiology - Renal Physiology
Volume316
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Benign prostatic hyperplasia
  • Inflammation
  • Interleukin-1β
  • Lower urinary tract symptoms
  • Mass spectrometry
  • Urine proteomics

ASJC Scopus subject areas

  • Physiology
  • Urology

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