Biomarkers of Exposure to Toxic Substances. Volume 3: Proteomics, Biomarkers to Kidney and Organ Damage

摘要

Early detection of kidney malfunction can help to prevent permanent kidney damage. During the normal physiological state, predominantly low molecular weight proteins pass freely through the glomerular barriers; whereas some middle range molecular weight (and almost no high molecular weight) proteins can get through the renal tubules. Consequently, negligible amounts of protein are excreted into the urine. However, strenuous activity can cause dehydration, decreased blood flow, as well as the build-up of toxic chemicals-- thereby multiplying the risk of kidney damage. Knowledge of urinary protein biomarkers would be ideal for the early detection of kidney malfunction/disease, since urine is readily available and easy to collect. As such, we utilized proteomic and metabonomic techniques (Liquid chromatography coupled to mass spectrometry, two dimensional difference in-gel electrophoresis) to monitor/quantitate changes in urinary protein abundance or post-translational modifications in the well established D-serine and puromycin nephrotoxin models. D-serine selectively damages renal proximal tubes in rodents, while puromycin causes transient visceral epithelial cell injury accompanied by heavy proteinuria. We observed numerous changes in levels of different proteins that can be very useful for early diagnostics of kidney malfunctions caused by different toxicants.