Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of metabolism affecting the last step of cholesterol biosynthesis. It is characterized by a deficiency of the enzyme 7-dehydrocholesterol reductase and accumulation of 7-dehydrocholesterol (7DHC) in cells and body fluids. Given the similarities between 7DHC and cholesterol, 7DHC can be incorporated into cell membranes in lieu of cholesterol. Nevertheless, due to their structural differences and distinct affinity to other membrane components, this substitution alters membrane properties and one can expect to find abnormalities in membrane protein composition. In order to identify differences in membrane proteins that could facilitate our understanding of SLOS physiopathology, we isolated detergent-resistant membranes (DRMs) from the skeletal muscle of Dhcr7T93M/T93M mice and C57/BL6 controls and performed comparative proteomic analysis using iTRAQ for peptide quantification. A total of 133 proteins were identified in the DRM fraction: 17 (13%) proteins demonstrated increased expression in SLOS mice, whereas, 21 (16%) showed decreased expression. Characterization of functional point of view and bioenergetics pathway and transmembrane transport responded to the major differences between the two groups of animals.
Part of the book: Cholesterol
Recently, proteomics has emerged as an important tool for understanding biological systems, protein–protein interactions, and networks that ultimately lead to a deeper understanding of the underlying mechanisms of certain diseases. More recently, the study of secretomes, a type of proteomics, has also been highlighted as a potential next step in the field of diagnosis/prognosis. The secretome is the set of proteins expressed by an organism and secreted into the extracellular space, comprising 13–20% of all proteins. Since almost all, if not all, organs produce secretomes, this means that it is possible to study secretomes and trace these proteins back to their origin, supporting the idea that this could indeed be very important in diagnosing certain diseases. This is often combined with techniques such as mass spectrometry to measure the secretome of, for example, a particular tissue, and bioinformatics tools and databases to give us an idea of what to expect (prediction). In this paper, we will give a general overview of this world, but with a focus on the new bioinformatics tools and databases, their advantages and disadvantages, as well as a deeper look at isolation systems for proteomes, specifically salivary secretomes. Indeed, the salivary secretome represents a valuable new tool capable of providing insights into immunopathology and potentially aiding in diagnostics. Furthermore, we will explore applications of these methods and give an idea of what the future holds for such promising techniques: Salivary secretome in conjunction with bioinformatics tools/databases in the diagnosis of diseases (such as diabetes, Sjogren’s syndrome, and cardiovascular disease).
Part of the book: Periodontology