The urine proteome as a biomarker of radiation injury

Abstract

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased postirradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury.

A study on the effect of the internal exposure to 210Po on the excretion of urinary proteins in rats

“…As a result, pathological changes in human organs that may be reflected in the blood plasma/serum may also be reflected and detected in the urinary proteome (Gonzalez-Buitrago et al 2007). In fact, the work presented here was inspired by a recent study by Sharma et al, where a total body X-ray irradiation (10 Gy) of rats showed a decrease in urinary excretion of albumin and immunoglobulins, but with a concomitant increase in alpha-1-acid glycoprotein (Sharma et al 2008). It was therefore interesting to investigate whether internal exposure from an alpha emitter produced similar changes to the expression of urinary protein biomarkers that could potentially be utilized as a screening tool for triaging an internal contamination in an R/N emergency.…”

“…There has been a renewed interest in studying urinary biomarkers to be used as a rapid screening tool for IR exposure in an R/N emergency. However, most of the recent studies have been focused on exposure to external radiation, such as gamma radiation (Lanz et al 2009;Tyburski et al 2009a, b;Johnson et al 2011Johnson et al , 2012) and X-rays (Sharma et al 2008(Sharma et al , 2010. The present study aims to investigate some urinary proteins as a possible clinical biomarker for internal exposure.…”

“…As it is composed of filtered plasma proteins, and proteins from the kidney and other genitourinary organs, urine proteome has been hypothesized to be a useful source of biomarkers for IR exposure (Pernot et al 2012;Sharma et al 2010). Both total body irradiation and local kidney irradiation of rats with a single 10-Gy dose of X-rays showed significant changes in urine proteome within 24 h after irradiation (Sharma et al 2008(Sharma et al , 2010. There has been a renewed interest in studying urinary biomarkers to be used as a rapid screening tool for IR exposure in an R/N emergency.…”

Automated Mass Spectrometry–Based Functional Assay for the Routine Analysis of the Secretome

“…Conversely, analysis of proteins from blood or urine will reflect the health not only of an organ (e.g., the health of the liver by measuring the activity of the blood transaminases) but also of the whole organism. 22,[25][26][27][28][29][30][31][32][33] Although a particular secreted molecule (and/or protein) may reveal information about a particular organ, a combination of secreted molecules (and/or proteins) may reflect the physiological state of a particular cell type, or of an organ or of the whole organism. Here we primarily discuss secreted proteins, as analyzed by mass spectrometry.…”

“…[1][2][3][4][5][6]8 Secretomes may be classified according to various criteria, such as the type of the cell or the type of the tissue producing the secretome, or the location of the secreted proteins such as extracellular but nonsystemic, intraorgan (e.g., intrahepatic) or extracellular but systemic, extraorgan (e.g., blood, saliva, urine, or lymphatic fluid). [16][17][18][19][20][21][22][23][24][25][26][27][28][29] Depending on the type of secretome analyzed, specific information may be obtained. For example, analysis of proteins secreted by cells grown in cell culture will reflect the health and activity of those cells.…”