Microarrays cellular

Keywords Microarray DNA microarray Carbohydrate microarray Protein microarray Antibody microarray G protein-coupled receptor microarray Cellular microarray Optical biosensor Resonant waveguide grating biosensor Surface plasmon resonance Dynamic mass redistribution... 

Examples of biomarker assays operating at different levels are given in Table 4.2. The recent development of omics technology should provide strong support to this approach (Box 4.3). Microarray analysis, for instance, can give a time-related sequence of gene responses that relate to the cellular changes of toxicity. 

The ultimate goal of microarray-based expression analysis is to acquire a comprehension of the entire cellular process, in order to exploit and to standardize the multidi-menisional relations between genotype and phenotype. However, an increasingly important parameter, which has not yet been substantially taken into account, is the role of cellular translation. This means that mRNA expression data need to be correlated with the assortment of proteins actually present in the cell. One approach is based on the use of microarrays containing double-stranded DNA probes for the analysis of DNA-protein interaction and, thus, the detection and identification of DNA-binding proteins by means of fluorescence [130] or mass spectrometry analysis [131]. Moreover, substantial efforts are currently under way to develop protein, antibody, or even cell arrays, applicable to the cor-... 

Amundson SA et al. Fluorescent cDNA microarray hybridisation reveals complexity and heterogeneity of cellular geno-toxic stress responses. Oncogene 1999 18 3666-3672. 

Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2 119-125... 

Gusterson BA, Ross DT, Ffeath VJ, Stein T (2005) Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res 7(4) 143 148 Ffsu FD, Nielsen TO, Alkushi A, Dupuis B, Huntsman D, Liu CL, van de Rijn M, Gilks CB (2002) Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochem istry. Mod Pathol 15 1374 1380... 

Fernandes T.G. Diogo M.M. Clark D.S. Dordick J.S. Cabral J. High-throughput cellular microarray platforms Applications in drug discovery, toxicology and stem cell research. Trends in Biotechnology, 2009, 27, 342-349. 

Expression analysis using DNA microarrays analyzes only the transcriptome it should be mentioned that mRNA abundance in a cell often correlates poorly with the amount of protein synthesized (27). Important regulation takes place at the levels of translation and enzymatic activities. The only effect of a signal transduction pathway that is observed in a gene expression experiment is that at the endpoint of a given pathway. DNA microarrays currently have little value in determining post-translational modifications, which influence the diversity, affinity, function, cellular abundance, and transport of proteins. 

The basal immunological mechanisms are complex but can now be analyzed with refined and more powerful laboratory methods, such as the microarray technique. With the help of this technique, additional information besides that concerning IgE and cytokine levels about the association between adaptive and innate immune response as well as other cellular responses can be gathered (6-8). 

A number of commercial antibody-based microarrays for multiplexed cytokines analysis are now available (Beckman Coulter BD Biosciences Panom-ics Pierce S S Zyomyx and others). Cytokines are essentially biomarkers of cell injury, inflammation, and apoptosis. They are released by cells in culture in response to drug action (Turtinen et al., 2004) or are elevated in serum in various disease states. Moreover, numerous cytokines are involved in cellular response and many serve as dual effectors (Asao and Fu, 2000). As a result, anticytokine microarrays are being evaluated in drug discovery for off-target toxicity testing to replace standard ELISA plate formats. 

The applicahon of the cDNA microarray revealed that the fungicide appeared to affect a number of cellular processes. While the content of the Clontech microarray was rather limited, it provided a substanhal amount of new informahon regarding amphotericin B-mediated cellular toxicity. 

This book picks up the array technology journey from the mid-1990s with the introduction of microarray-based gene expression analysis. The global analysis of genes by microarrays has provided a fresh and exciting view of the cellular process. More importantly, it enabled others to consider similar utility in various "omic" fields. Hence, we have witnessed the emergence of protein arrays to address proteomics. 

The family of HDAC enzymes has been named after their first substrate identified, i.e., the nuclear histone proteins. Histone proteins (H2A, H2B, H3 and H4) form an octamer complex, around which the DNA helix is wrapped in order to establish a condensed chromatin structure. The acetylation status of histones is in a dynamic equilibrium governed by histone acetyl transferases (HATs), which acetylate and HDACs which are responsible for the deacetylation of histone tails (Fig. 1). Inhibition of the HDAC enzyme promotes the acetylation of nucleosome histone tails, favoring a more transcriptionally competent chromatin structure, which in turn leads to altered expression of genes involved in cellular processes such as cell prohferation, apoptosis and differentiation. Inhibition of HDAC activity results in the activation of only a limited set of pre-programmed genes microarray experiments have shown that 2% of all genes are activated by structmally different HDAC inhibitors [1-5]. In recent years, a growing number of additional nonhistone HDAC substrates have been identified, which will be discussed in more detail below. 

Tourniaire G, Colhns J, Campbell S, Mizomoto H, Ogawa S, Thaburet J-F, Bradley M (2006) Polymer microarrays for cellular adhesion. Chemical Commun 2118-2120... 

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