DOI: 10.1097/SA.0b013e318033647b
,
Issn Print: 0039-6206
Publication Date: 2007/04/01
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Excerpt
Joshua H. Atkins,*† and Jonas S. Johansson*‡
(Anesth Analg, 102:1207-1216, 2006)
Departments of *Anesthesiology and Critical Care and †Biochemistry and Biophysics; and the ‡Eldridge Reeves Johnson Research Foundation, University of Pennsylvania, Philadelphia, PA.
Drugs used in daily practice aim at proteins, not genes, by blocking ion channels, membrane receptors, and enzymes. Gene therapy, considered by many to be the future of medicine, therefore, turns the production of specific proteins on or off with exacting biochemical control. An understanding of proteins is vital for anesthesiologists, whose drugs affect total body function, including the balance of protein functions and expressions. Research technologies in proteomics will have an impact in operating rooms, intensive care units, and chronic pain clinics. Anesthesiologists must understand the emerging technology and its applications.
Proteomics is the effort to create technologies and bioinformatic methods to process large numbers of samples simultaneously with the goal of creating a protein map. Such a map can enhance the development of targeted molecular therapies for diseases and the precise characterization of physiological states as unconsciousness from general anesthesia or prolonged illness. Proteomics has also contributed to the trend of novel drug therapies and diagnostic reagents being protein-based.
New technologies are emerging to aid in the understanding of all protein science. Protein purification methods provide larger quantities of desired products with increasing efficiency. Proteins can be separated based on polarity or molecular weight; specific binding moieties can be incorporated onto a resin to allow separation of substrates. Molecules can be separated based on their mass-to-charge ratio using only very small amounts of material. New chromatography systems can separate proteins based on their overall hydrophobicity. As the numbers of purified proteins increase, the application of DNA-based microarray technology to protein analysis has also increased. The microarrays are small silicon wafers to which small concentrations of biologic material are attached. The material is screened for an interaction with another DNA strand, small molecule, or protein. Thousands of microexperiments can be performed simultaneously with the interactions then characterized by computer analysis. From these results, gene mutations could possibly be discovered by screening techniques using protein chips.
Mass spectrometry (MS), electrospray ionization, matrix-assisted and surface-enhanced laser desorption ionization time-of-flight and tandem MS (MS/MS) are among the many technologies being used in these studies. These techniques offer tools for studying proteins in real and simulated environments. Mass spectrometry allows rapid analysis of complex mixtures for protein composition. The newer MS techniques use gentler ionization methods to volatilize small quantities of macromolecules embedded in a solid matrix. This allows large molecules (eg, proteins) to be identified as the parent molecule rather than complex fragments.
With all the new technologies, the development of software products and international databases for the analysis of computer-generated proteomic data has emerged. These programs must be able to standardize data sets across experiments, technology platforms, and physiological/biochemical systems. A systematic approach to identifying proteins and changes in protein expression is also needed. Artificial neural networks have been used in genomic analysis of microarray data and are now being studied for applications to proteomics. Computers are programmed as neurons to mimic brain processing of data and to recognize patterns that will allow generalizations and predictions to be made based on the patterns seen in the raw data.
The results of proteomic studies can have practical results and applications. Protein expression in diseases (eg, prostate, breast, and colorectal cancers) is known, and protein profiling in cardiovascular, hepatic, and pulmonary diseases is underway. However, applications of proteomic technology in anesthesia have been limited.
