Proteome alterations in response to aristolochic acids in experimental animal model.

J Proteomics

Proteomics Core, COBRE Center for Cancer Research Development, Rhode Island Hospital, Providence, RI, USA.

Published: December 2012

AI Article Synopsis

  • The study investigates the impact of dietary poisoning with aristolochic acids (AA) on Endemic Nephropathy (EN) and related cancers, revealing significant changes in the urinary proteome of AA-treated mice.
  • Researchers utilized a mixed method of gel-based and in-solution tryptic digestion alongside LC-ESI-MS/MS to analyze the proteomes from urine, plasma, and kidney tissue.
  • Findings identified key proteins linked to kidney health and inflammation that may serve as potential biomarkers for EN and associated urinary tract cancers in humans.

Article Abstract

Strong indications have been presented that dietary poisoning with aristolochic acids (AA) is responsible for Endemic Nephropathy (EN) and AA associated cancer of the upper urinary tract (UUTC). Our recent investigation showed drastic urinary proteome changes in AA treated mice. This study was designed to identify proteome changes associated with AA nephrotoxicity in experimental animal model. The DBA and C57BL mice, which differ in AA sensitivity, were exposed to AA for 4 days. The strategy for urinary, plasma and kidney tissue proteome study of AA exposed and control mice integrated gel-based and in-solution tryptic digestion combined with LC-ESI-MS/MS. To maximize proteome coverage, plasma fractionation scheme was developed and MS compatible sequential tissue extraction procedure was established. Proteomic analyses of urinary, plasma and kidney tissue tryptic digests resulted in identification of several cytoskeletal proteins, as well as proteins involved in kidney development and inflammatory response, that are differentially expressed in both AA exposed and control mice. These proteins are consistent with renal pathogenesis of endotoxicity and cancer. This proteomic strategy could be effectively translated for unbiased discovery of potential biomarkers for EN and associated UUTC in humans. At the same time, these results highlight the significance of AA exposure with EN. This article is part of a Special Issue entitled: Integrated omics.

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http://dx.doi.org/10.1016/j.jprot.2012.06.026DOI Listing

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