Proteome alterations in response to aristolochic acids in experimental animal model.
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.
Proteomics Core, COBRE Center for Cancer Research Development, Rhode Island Hospital, Providence, RI, USA.
Marijana
M
Rucevic
Thomas
T
Rosenquist
Lucas
L
Breen
Lulu
L
Cao
James
J
Clifton
Douglas
D
Hixson
Djuro
D
Josic
D000818:Animals; D034341:Aristolochic Acids / Q000009:adverse effects* / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000652:urine; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009153:Mutagens / Q000009:adverse effects* / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000097:blood / Q000652:urine; D009374:Neoplasms, Experimental; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D014571:Urologic Neoplasms / Q000097:blood / Q000139:chemically induced / Q000652:urine
D034341:Aristolochic Acids; D014408:Biomarkers, Tumor; D009153:Mutagens; D009363:Neoplasm Proteins; D020543:Proteome; C000228:aristolochic acid I