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Krishnan S Kiang JG Fisher CU Nambiar MP Nguyen HT Kyttaris VC Chowdhury B Rus V Tsokos GC 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(5):3417-3423
T cells isolated from patients with systemic lupus erythematosus (SLE) express low levels of CD3zeta-chain, a critical molecule involved in TCR-mediated signaling, but the involved mechanisms are not fully understood. In this study we examined caspase-3 as a candidate for cleaving CD3zeta in SLE T cells. We demonstrate that SLE T cells display increased expression and activity of caspase-3. Treatment of SLE T cells with the caspase-3 inhibitor Z-Asp-Glu-Val-Asp-FMK reduced proteolysis of CD3zeta and enhanced its expression. In addition, Z-Asp-Glu-Val-Asp-FMK treatment increased the association of CD3zeta with lipid rafts and simultaneously reversed the abnormal lipid raft preclustering, heightened TCR-induced calcium responses, and reduced the expression of FcRgamma-chain exclusively in SLE T cells. We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3zeta-chain and suggest that such molecules can be considered in the treatment of this disease. 相似文献
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Rauen T Benedyk K Juang YT Kerkhoff C Kyttaris VC Roth J Tsokos GC Tenbrock K 《The Journal of biological chemistry》2011,286(37):32366-32372
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Dendroulakis V Russell BS Eric Elmquist C Trudel LJ Wogan GN Deen WM Dedon PC 《Nitric oxide》2012,27(3):161-168
Nitric oxide (NO) plays key roles in cell signaling and physiology, with diverse functions mediated by NO concentrations varying over three orders-of-magnitude. In spite of this critical concentration dependence, current approaches to NO delivery in vitro result in biologically irrelevant and poorly controlled levels, with hyperoxic conditions imposed by ambient air. To solve these problems, we developed a system for controlled delivery of NO and O(2) over large concentration ranges to mimic biological conditions. Here we describe the fabrication, operation and calibration of the delivery system. We then describe applications for delivery of NO and O(2) into cell culture media, with a comparison of experimental results and predictions from mass transfer models that predict the steady-state levels of various NO-derived reactive species. We also determined that components of culture media do not affect the steady-state levels of NO or O(2) in the device. This system provides critical control of NO delivery for in vitro models of NO biology and chemistry. 相似文献
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Stavropoulos-Kalinoglou A Metsios GS Panoulas VF Douglas KM Nevill AM Jamurtas AZ Kita M Koutedakis Y Kitas GD 《Arthritis research & therapy》2008,10(3):R59