The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Chaitan Khosla - One of the best experts on this subject based on the ideXlab platform.
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thiol disulfide exchange reactions in the mammalian Extracellular Environment
Annual Review of Chemical and Biomolecular Engineering, 2016Co-Authors: Chaitan KhoslaAbstract:Disulfide bonds represent versatile posttranslational modifications whose roles encompass the structure, catalysis, and regulation of protein function. Due to the oxidizing nature of the Extracellular Environment, disulfide bonds found in secreted proteins were once believed to be inert. This notion has been challenged by the discovery of redox-sensitive disulfides that, once cleaved, can lead to changes in protein activity. These functional disulfides are twisted into unique configurations, leading to high strain and potential energy. In some cases, cleavage of these disulfides can lead to a gain of function in protein activity. Thus, these motifs can be referred to as switches. We describe the couples that control redox in the Extracellular Environment, examine several examples of proteins with switchable disulfides, and discuss the potential applications of disulfides in molecular biology.
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Thiol–Disulfide Exchange Reactions in the Mammalian Extracellular Environment
Annual review of chemical and biomolecular engineering, 2016Co-Authors: Chaitan KhoslaAbstract:Disulfide bonds represent versatile posttranslational modifications whose roles encompass the structure, catalysis, and regulation of protein function. Due to the oxidizing nature of the Extracellular Environment, disulfide bonds found in secreted proteins were once believed to be inert. This notion has been challenged by the discovery of redox-sensitive disulfides that, once cleaved, can lead to changes in protein activity. These functional disulfides are twisted into unique configurations, leading to high strain and potential energy. In some cases, cleavage of these disulfides can lead to a gain of function in protein activity. Thus, these motifs can be referred to as switches. We describe the couples that control redox in the Extracellular Environment, examine several examples of proteins with switchable disulfides, and discuss the potential applications of disulfides in molecular biology.
Filomena G Ottaviano - One of the best experts on this subject based on the ideXlab platform.
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redox regulation in the Extracellular Environment
Circulation, 2008Co-Authors: Filomena G Ottaviano, Diane E Handy, Joseph LoscalzoAbstract:The oxidizing nature of the Extracellular Environment is vastly different from the highly reducing nature of the intracellular compartment. The redox potential of the cytosolic compartment of the intracellular Environment limits disulfide bond formation, whereas the oxidizing Extracellular Environment contains proteins rich in disulfide bonds. If not for an Extracellular antioxidant system to eliminate reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation would become excessive, resulting in cellular damage. Many reviews have focused on the role of intracellular antioxidants in the elimination of oxidative stress, but this one will focus on the coordinated action of both intracellular and Extracellular antioxidants in limiting cellular oxidant stress.
Joseph Loscalzo - One of the best experts on this subject based on the ideXlab platform.
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redox regulation in the Extracellular Environment
Circulation, 2008Co-Authors: Filomena G Ottaviano, Diane E Handy, Joseph LoscalzoAbstract:The oxidizing nature of the Extracellular Environment is vastly different from the highly reducing nature of the intracellular compartment. The redox potential of the cytosolic compartment of the intracellular Environment limits disulfide bond formation, whereas the oxidizing Extracellular Environment contains proteins rich in disulfide bonds. If not for an Extracellular antioxidant system to eliminate reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation would become excessive, resulting in cellular damage. Many reviews have focused on the role of intracellular antioxidants in the elimination of oxidative stress, but this one will focus on the coordinated action of both intracellular and Extracellular antioxidants in limiting cellular oxidant stress.
Antonio De Maio - One of the best experts on this subject based on the ideXlab platform.
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hsp70 translocates into the plasma membrane after stress and is released into the Extracellular Environment in a membrane associated form that activates macrophages
Journal of Immunology, 2008Co-Authors: Virginia L Vega, Monica Rodriguezsilva, Tiffany Frey, Mathias Gehrmann, Juan Carlos Diaz, Claudia Steinem, Gabriele Multhoff, Nelson Arispe, Antonio De MaioAbstract:Heat shock proteins (hsps) are intracellular chaperones that play a key role in the recovery from stress. Hsp70, the major stress-induced hsp, has been found in the Extracellular medium and is capable of activating immune cells. The mechanism involved in Hsp70 release is controversial because this protein does not present a consensual secretory signal. In this study, we have shown that Hsp70 integrates into artificial lipid bilayer openings of ion conductance pathways. In addition, this protein was found inserted into the plasma membrane of cells after stress. Hsp70 was released into the Extracellular Environment in a membrane-associated form, sharing the characteristics of this protein in the plasma membrane. Extracellular membranes containing Hsp70 were at least 260-fold more effective than free recombinant protein in inducing TNF-alpha production as an indicator of macrophage activation. These observations suggest that Hsp70 translocates into the plasma membrane after stress and is released within membranous structures from intact cells, which could act as a danger signal to activate the immune system.
Andrei Kogan - One of the best experts on this subject based on the ideXlab platform.
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The Role of Extracellular Environment in Regulation of Cellular Response to Electric Field
Biophysical Journal, 2014Co-Authors: Toloo Taghian, Abdul Q. Sheikh, Daria A. Narmoneva, Andrei KoganAbstract:Chronic wounds impose a significant burden on patients and health care system because they do not effectively respond to pharmacological treatments. Developing new non-pharmacological treatments requires application of advanced technology to control natural cell signals to trigger the desired cell responses. Electric field (EF) generated in the ionic Environment surrounding cells and cell membrane has been shown to control cell behaviors. Therefore, manipulation of this EF by external EF may provide a new non-chemical treatment. EF-cell interactions may be affected by both the distribution of the induced EF within the cell and the properties of the Extracellular matrix (ECM), which is known to regulate cell response to the external stimuli. Therefore, mechanistic studies of cell-ECM interaction in response to EF are essential for the efficient control of cell responses and development of EF-based therapies. To address this issue, we developed a combined theoretical-experimental approach. Theoretical 3D EF-cell interaction model solves Maxwell's equations (ANSOFT_HFSS) for a membrane-enclosed hemisphere subjected to EF in its native configuration to provide a precise distribution of induced EF within the cell in wide frequency range. Simulation results predict a frequency specific cell response. At low frequency EF is confined in cell membrane and expected to regulate membrane-initiated responses. At high frequency EF penetration into the cell increases and is therefore expected to activate intracellular interactions. Experimentally measured responses of endothelial cells to EF confirm this prediction. Analysis of growth factor expression and capillary morphogenesis show a significant difference between low and high frequency groups. Blocking membrane receptors does not affect observed responses in high frequency, which confirms activation of intracellular interaction. We showed that cell responses to EF function differently in natural versus synthetic ECM. We attribute this to difference in ECM properties.
