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8-OH-dG: A novel immune activator.
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Innate immunity against viral or pathogenic infection involves sensing of non-self-molecules, otherwise known at pathogen-associated molecular patterns (PAMPs). This same sensing mechanism can be applied to damaged self-molecules, which are called damage-associated molecular patterns (DAMPs). One type of molecular pattern, for both groups, is cytosolic or extracellular DNA. However, there is not an extensive amount of research showing specifically what type of DAMP DNA molecule is best at activating this immune sensing response. A recent study investigated the mechanism behind how oxidized DNA from UV damage activates an immune sensing response.
A group of researchers found that, compared to a variety of types of cellular damage, damage from UV irradiation created a strong immune response (type I IFN response), seen across different types of immune regulatory cells. This was compared with freeze/thaw, physical damage and nutritional deprivation, each of which did not produce a noticeable immune response. Additionally, this immune response was seen when DNA was exposed to UV-A and UV-B (the type of radiation produced by our sun) and UV-C radiation.
DNA can be damaged by UV light directly, or through reactive oxygen species (ROS) caused by UV light. A well-known mark of DNA damaged by ROS is the oxidation of guanine to create 8-hydroxyguanine (8-OH-dG). These researchers saw an increase in 8-OH-dG dependant on the level of UV dose, and this also correlated with an increase in immune response; showing that DNA damage created by UV light in the form of 8-OH-dG is sufficient to activate an immune response. This study shows that 8-OH-dG can be classified at a DAMP.
Next, this group wanted to place a mechanism to these observations. They found that the ability of oxidation-damaged DNA to activate an immune response was dependant on cGAS and STING. Free DNA in the cytosol binds cGAS, a cGAMP synthase. This action produces a messenger molecule which proceeds to bind to and activate STING, an endoplasmic reticulum protein. STING activation will ultimately stimulate a type I IFN response.
When a cell’s own DNA is damaged, the cell’s machinery does all it can to repair it. This sometimes involves erasing, or degrading, the DNA that has been damaged. The enzyme, TREX1 exonuclease, has this job in a cell. However, this group found that when DNA was modified with an 8-OH-dG, it was resistant to this degradation by TREX1. This implies that the observed increase in immune response due to the presence of 8-OH-dG occurred because of an accumulation of damaged DNA, because it was not being degraded by TREX1 and could therefore sufficiently activate cGAS and STING.
This type of study has important implications for autoimmune diseases like lupus erythematosus (LE), which is characterized by its abnormally high number of autoantibodies against DNA. It is possible that this uncontrollable immune response is activated by oxidation-damaged DNA. Studies in this area, therefore, hold great importance.
ELISA Kits, Antibodies, Proteins, and Reagents for Life Scientists
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Our aim at ebiohippo is to facilitate and accelerate access to health for people everywhere. Through our life science products, we offer solutions for diagnostics and environmental testing as well. We aim to help scientists and engineers solve problems at every stage of their work. The provided lab materials, technologies, and services will help make research, and production, both pharmaceutical and biotech, simpler, faster, and safer. AT ebiohippo, we believe that we can enable scientific discovery by helping customers understand biological functions and diseases. ebiohippo works in partnership with the global scientific community to offer superior products and solutions, both for research, and for manufacturing of chemical and biological drugs.
ebiohippo aims to help you advance in life sciences with high-quality training and support. We can help your highly interdisciplinary bioscience research, from the molecular level, through the cellular and organism levels, as well as spans bacteria, viruses, fungi, animals, and plants. Live science research deals with a broad range of biology, biotechnology, genomics, proteomics, bioinformatics, pharmaceutical and biomedical research, and techniques. We provide you with the products that allow you to identify common principles that operate across the breadth of living systems and investigate solutions to major global challenges. Our products are used in research done with cutting-edge computational and experimental technologies in the life sciences research sector.
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Our ELISA kits contain pre-coated antibody-plates, detection antibodies, buffers, diluents, standards, and substrates. All our kits are ready to use and we offer different formats to choose from including quantitative, semi-quantitative, indirect, or competitive. Along with that, our extensive catalog comprises of ELISA kits that can be used to study diverse biochemical pathways and diseases, such as cancer, the insulin pathway, and oxidative stress. Moreover, our kits are only assembled when you place an order to ensure that all of the components will be fresh and to extend the shelf life for our customers.
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Our kits are easy to use yet robust for life science research and bioassays, and are optimized for use on our instruments. They can easily measure enzyme activity, monitor and signal pathway activity, detect and quantify cellular progress such as cell death, cell viability or metabolic reactions. The constituents of every kit are thoroughly tested for their compatibility with each other to give you accurate and authentic results.
Additionally, with our offered assay kits, you’ll be able to study changes in gene expression, and to screen small molecule inhibitors. At ebiohippo, we offer kits that allow researchers to quickly narrow down results by detection target, species reactivity, application or conjugate, and with them, you can obtain highly sensitive, detailed, and accurate results across a wide dynamic range with fast, efficient processing.
At ebiohippo, we offer thousands of monoclonal/polyclonal antibodies and conjugates validated for use in a variety of common applications including WB, FC, IHC, ICC, IF, IP, and more. Our primary antibodies are developed as polyclonal or monoclonal, which use mouse, rat, rabbit, goat, and other animal species as hosts. The primary antibodies provided by us are produced and supplied in various forms, ranging from crude antiserum to antigen-purified preparations. We also offer you a superior antigen recognition system which is combined with the specificity and consistency of a monoclonal, bringing you the highest quality antibodies possible.
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With the diverse protein and peptide sources available at ebiohippo, we believe we can fulfill biochemical research needs with ease. The biomolecules we provide can fulfill a diverse range of roles, such as development factors and cytokines for cell culture, active enzymes for biochemical assays, carrier proteins for movement of molecules, inhibitors for blocking pathways, and antigens for use with antibodies. Furthermore, we also deal with ready-to-use commercial proteins or peptides that can save a great deal of time and effort. The suppliers we deal with often provide a measure of purity, typically with SDS-PAGE. The recombinant protein search tool offered at ebiohippo gives you the ability to browse through the entire catalog of proteins and peptides from a variety of suppliers. Whereas, our recombinant proteins are purified from E. coli, mammalian cells, and even from cell-free methods.