Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have been investigating the potential utility of engineered cell lines as surrogates for primary islet cells in treatment of type 1 diabetes. To this end, two strategies that have emerged for procuring cell lines with resistance to immune-mediated damage are 1) selection of cytokine-resistant cell lines by growth of INS-1 insulinoma cells in iteratively increasing concentrations of interleukin (IL)-1beta + gamma-interferon (IFN-gamma), and 2) stable overexpression of the anti-apoptotic gene bcl-2 in INS-1 cells. Herein, we show that bcl-2-overexpressing cells are resistant to the cytotoxic effects of reactive oxygen and nitrogen species (ROS/RNS), but are only modestly protected against high concentrations of IL-1beta + INF-gamma, whereas the converse is true in cytokine selected cells. We also found that the combination of bcl-2 expression and cytokine selection confers a broader spectrum of resistance than either procedure alone, such that the resultant cells are highly resistant to cytokines and ROS/RNS, with no impairment in glucose-stimulated insulin secretion. INS-1-derived cells with combined bcl-2 expression and cytokine selection are also more resistant to damage induced by coculture with mitogen-activated peripheral blood mononuclear cells. Surprisingly, application of the cytokine selection procedure to bcl-2-overexpressing cells does not result in impairment of nuclear factor-kappaB translocation, iNOS expression, and NO production, as clearly occurs upon application of the selection procedure to cells without bcl-2 overexpression. Further investigation of the diverse pathways involved in the development of cytokine and ROS/RNS resistance may define simplified and specific strategies for preservation of beta-cell mass.
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PMID:Discrete and complementary mechanisms of protection of beta-cells against cytokine-induced and oxidative damage achieved by bcl-2 overexpression and a cytokine selection strategy. 1276 53

Peroxynitrite (ONOO(-)) and hypochlorous acid (HOCl) are two highly reactive oxygen species generated in biological systems. The overproduction of peroxynitrite or hypochlorous acid is implicated in a broad array of human pathologies including vascular, immunological, and neurodegenerative diseases. However, unambiguous detection of these reactive oxygen species has been relatively difficult due to their short biological half-lives and multiple reaction pathways. Based on their specific chemical reactions, we have developed fluorescent probes HKGreen-1 and HKOCl-1 for highly sensitive detection of peroxynitrite and hypochlorous acid, respectively. Both probes have been demonstrated to be able to discriminate corresponding reactive species from other reactive oxygen and nitrogen species (ROS and RNS) in not only chemical systems but also biological systems. The endogenous production of peroxynitrite in neuronal cells under oxygen-glucose deprivation (OGD) conditions has been visualized for the first time by utilizing HKGreen-1 probe, whilst the endogenous production of hypochlorous acid in macrophage cells upon stimulation with LPS, IFN-gamma, and PMA has been imaged by utilizing HKOCl-1 probe.
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PMID:Synthetic fluorescent probes for imaging of peroxynitrite and hypochlorous acid in living cells. 1995 25

Macrophages produce reactive oxygen and nitrogen species (ROS/RNS) in response to immunological challenges. We have previously reported the real-time detection and quantification of released ROS/RNS by immunostimulated macrophages using constant potential amperometry, at four different potentials, with platinized carbon microelectrodes. As a methodological extension to that work, we sought to develop an electroanalytical method that would allow for the simultaneous monitoring of several ROS/RNS. Triple potential-step chronoamperometry at platinized carbon microelectrodes was found to provide satisfactory sensitivity and signal/noise ratio for this purpose. The title method was applied to the detection of endogenously produced ROS/RNS by single IFN-gamma/LPS/PMA stimulated RAW 264.7 macrophages. Significantly higher fluxes of H(2)O(2), ONOO(-), and NO* responses were detected over stimulated macrophages as compared to unactivated macrophages, consistent with the endogenous production of primary NO* and O(2)(*-) by both the inducible isoform of nitric oxide synthase (iNOS) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymatic systems in stimulated cells. Crucially, significant temporal variations in the release of each of the aforementioned species was evidenced using this method, which would not have been achievable with the use of either constant potential amperometry or classical biochemical methods such as the Griess assay.
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PMID:Simultaneous detection of reactive oxygen and nitrogen species released by a single macrophage by triple potential-step chronoamperometry. 2010 64