The role of toxicoproteomics in assessing organ specific toxicity

Merrick, B. Alex; Witzmann, Frank A.

doi:10.1007/978-3-7643-8336-7_13

Cited by 21 publications

(22 citation statements)

References 138 publications

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“…Such complexity arises due to alternative splicing of mRNA, post-translational modifications, wide dynamic range and differential protein stability, along with a variety of other issues related to the technology and the biological systems employed. As proteomics is employed for a variety of research purposes, the approaches that have evolved are quite diverse and involve different levels of technical maturity/difficulty and expense [81]. For a more in-depth discussion of the application of proteomics to toxicology research, the reader is referred to two excellent reviews [81,82].…”

Section: Proteomicsmentioning

confidence: 99%

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The Application of Omics Technologies to the Study of Mammalian Toxicology

Auerbach¹,

Merrick²

2015

Mammalian Toxicology

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Section: Proteomicsmentioning

confidence: 99%

“…As proteomics is employed for a variety of research purposes, the approaches that have evolved are quite diverse and involve different levels of technical maturity/difficulty and expense [81]. For a more in-depth discussion of the application of proteomics to toxicology research, the reader is referred to two excellent reviews [81,82].…”

Section: Proteomicsmentioning

confidence: 99%

The Application of Omics Technologies to the Study of Mammalian Toxicology

Auerbach¹,

Merrick²

2015

Mammalian Toxicology

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“…Therefore, strict regulation of chemokine activity is crucial [127]. The overall impact of cleaved chemokines in cellular responses is an area of active research, as well as is the role of toxicoproteomics in assessing organ-specific toxicity [32,128].…”

Section: Advantages Of Iace Over Other Immunoassaysmentioning

confidence: 99%

Immunoaffinity capillary electrophoresis: A new versatile tool for determining protein biomarkers in inflammatory processes

Guzman¹,

Phillips

2011

Electrophoresis

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Many diseases caused by inflammatory processes can progress to a chronic state causing deterioration in the quality of life and a poor prognosis for long-term survival. To address inflammatory diseases effectively, early detection and novel therapeutics are required. However, this can be challenging, in part because of the lack of early predictive biomarkers and the limited availability of adequate technologies capable of the identification/characterization of key predictive biomarkers present in biological materials, especially those found at picomolar concentrations and below. This review highlights the need for state-of-the art methodologies, with high-sensitivity and high-throughput capabilities, for determination of multiple biomarkers. Although many new biomarkers have been discovered recently, existing technology has failed to successfully bring this advancement to the patient's bedside. We present an overview of the various advances available today to extend the discovery of predictive biomarkers of inflammatory diseases; in particular, we review the technology of immunoaffinity capillary electrophoresis (IACE), which combines the use of antibodies as highly selective capture agents with the high resolving power of capillary electrophoresis. This two-dimensional hybrid technology permits the quantification and characterization of several protein biomarkers simultaneously, including subtle structural changes such as variants, isoforms, peptide fragments, and post-translational modifications. Furthermore, the results are rapid, sensitive, can be performed at a relatively low cost, without the introduction of false positive or false negative data. The IACE instrumentation can have relevance to medical, pharmaceutical, environmental, military, cultural heritage (authenticity of art work), forensic science, industrial and research fields, and in particular as a point-of-care biomarker analyzer in translational medicine.

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“…Since proteins constitute both structural and functional infrastructures of tissues, their changes can have adverse biological consequences affecting growth, differentiation, survival, and signaling mechanisms of the cells. Thus, a major goal of toxicoproteomics has been to characterize biochemical changes that lead to disease processes that can be intervened (Kennedy, 2002;Merrick and Witzmann, 2009;Usami et al, 2009). The objective of this study was to find how thiram affects chondrocyte proteome that may explain their premature death leading to the development of TD.…”

Section: Introductionmentioning

confidence: 99%

Effect of thiram on avian growth plate chondrocytes in culture

Rasaputra

Liyanage²,

Lay³

et al. 2013

J. Toxicol. Sci.

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-Thiram is a dithiocarbamate pesticide that causes tibial dyschondroplasia (TD), a growth plate defect, in poultry. Deaths of transitional zone chondrocytes appear to interrupt endochondral bone development leading to the broadening of growth plate. The mechanism of action of thiram on chondrocytes is not well understood. Since proteins play major roles in different aspects of cell's metabolism, growth, and survival, the objective of this study was to find whether thiram produces proteomic changes that could impair the development of chondrocytes. The chondrocytes, isolated from proximal tibial growth plates, were cultured with or without a sub-lethal concentration of thiram for 48 hr, and the cell proteins were extracted, and subjected to 2-D gel electrophoresis. The gel images were compared and statistically evaluated using Melanie software to identify differentially expressed protein spots. Of a total of 72 identifiable spots 3 were down-regulated and 2 up-regulated in thiram treated chondrocytes. In-gel trypsin digestion of the protein spots followed by their characterization by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry identified 25 spots comprising of 23 proteins. Two of 3 down-regulated proteins were identified as a heat shock protein 70 (HSP 70) and a GALE (UDP-galactose-4 epimerase) protein isoform I. The up-regulated proteins were Serpin H1, a protein involved in collagen metabolism and a redox sensor NmrA-like (NMRAL) family domain protein-1. Both GALE and NMRAL proteins are implicated in energy metabolism and redox regulation whereas the HSP 70 protects cells against stress, and implicated in chondrocyte hypertrophy, an important event in endochondral bone formation. The failure of chondrocyte protective mechanisms such as associated with protection against cellular stress and energy metabolism appear to be the likely cause for chondrocyte death induced by thiram.

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The role of toxicoproteomics in assessing organ specific toxicity

Cited by 21 publications

References 138 publications

The Application of Omics Technologies to the Study of Mammalian Toxicology

The Application of Omics Technologies to the Study of Mammalian Toxicology

Immunoaffinity capillary electrophoresis: A new versatile tool for determining protein biomarkers in inflammatory processes

Effect of thiram on avian growth plate chondrocytes in culture

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