Vol 12: Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review.Report as inadecuate



 Vol 12: Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review.


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This article is from Proteome Science, volume 12.AbstractScientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide LPS endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response APR following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins APP and micro-ribonucleic acids miRNAs in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis 2-DE coupled with either matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry MALDI-TOF MS or liquid chromatography–mass spectrometry LC-MS-MS are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS-MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra SWATH approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay ELISA, quantitative real-time polymerase chain reaction qRT-PCR, and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing NGS are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future.



Author: Chemonges, Saul; Tung, John-Paul; Fraser, John F

Source: https://archive.org/







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