The Experts below are selected from a list of 132 Experts worldwide ranked by ideXlab platform
Francine Rendu - One of the best experts on this subject based on the ideXlab platform.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca(2+) signals, release reaction, and a(IIb)beta(3) integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent a(IIb)beta(3) activation by agonists. Thiosulfinates increased the basal intracellular Ca(2+) level of platelets. In activated platelets, they markedly inhibited the Ca(2+) mobilization independently of the external Ca(2+), the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
Perrine Badol - One of the best experts on this subject based on the ideXlab platform.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca(2+) signals, release reaction, and a(IIb)beta(3) integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent a(IIb)beta(3) activation by agonists. Thiosulfinates increased the basal intracellular Ca(2+) level of platelets. In activated platelets, they markedly inhibited the Ca(2+) mobilization independently of the external Ca(2+), the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
James N. Siedow - One of the best experts on this subject based on the ideXlab platform.
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Changes in the redox state of the alternative oxidase regulatory Sulfhydryl/disulfide system during mitochondrial isolation: implications for inferences of activity in vivo
Plant Science, 1997Co-Authors: Ann L. Umbach, James N. SiedowAbstract:Abstract The cyanide-resistant alternative oxidase of plants exists as a homodimer in the inner mitochondrial membrane. When the subunits of the dimer are connected by an intermolecular disulfide bond, the enzyme is relatively inactive. When this bond is reduced to its constituent Sulfhydryls, the enzyme becomes more active and can be further activated by α-keto acids. We have attempted to correlate the proportions of oxidized and reduced alternative oxidase with the physiological state of the plant by using immunoblots to visualize the ratio of alternative oxidase species present. However, during the process of mitochondrial isolation from Sauromatum guttatum and Glycine max, the alternative oxidase underwent oxidation of the intermolecular Sulfhydryl/disulfide system with the result that the proportion of oxidized and reduced alternative oxidase species in isolated mitochondria differed from that of the starting plant material. The presence of the Sulfhydryl reagents, N-ethylmaleimide and iodoacetate, during mitochondrial isolation prevented alternative oxidase Sulfhydryl/disulfide oxidation, but also led to reduction of the oxidized protein species. Thus, it appears not possible to determine the redox state of the alternative oxidase Sulfhydryl/disulfide system in vivo. Further, due to the spontaneous formation of the oxidized alternative oxidase species during isolation, alternative oxidase activity will be less in isolated mitochondria than in the plant tissue from which the mitochondria were derived.
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The reaction of the soybean cotyledon mitochondrial cyanide-resistant oxidase with Sulfhydryl reagents suggests that alpha-keto acid activation involves the formation of a thiohemiacetal.
Journal of Biological Chemistry, 1996Co-Authors: Ann L. Umbach, James N. SiedowAbstract:The cyanide-resistant alternative oxidase of plant mitochondria is known to be activated by alpha-keto acids, such as pyruvate, and by the reduction of a disulfide bond that bridges the two subunits of the enzyme homodimer. When the regulatory cysteines are oxidized, the inactivated enzyme is much less responsive to pyruvate than when these groups are reduced. When soybean cotyledon mitochondria were isolated in the presence of iodoacetate or N-ethylmaleimide, the intermolecular disulfide bond did not form and the alternative oxidase was present only as a noncovalently associated dimer. N-Ethylmaleimide inhibited alternative oxidase activity, but iodoacetate was found to stimulate activity much like pyruvate, including enhancing the enzyme's apparent affinity for reduced ubiquinone. The presence of pyruvate or iodoacetate blocked inhibition of the enzyme by N-ethylmaleimide, indicating that all three compounds acted at the same Sulfhydryl group on the alternative oxidase protein. The site of pyruvate and iodoacetate action was shown to be a different Sulfhydryl than that involved in the redox-active regulatory disulfide bond, because iodoacetate bound to the alternative oxidase at the activating site even when the redox-active regulatory Sulfhydryls were oxidized. Given the nature of the covalent adduct formed by the reaction of iodoacetate with Sulfhydryls, the activation of the alternative oxidase by alpha-keto acids appears to involve the formation of a thiohemiacetal.
Monique David-dufilho - One of the best experts on this subject based on the ideXlab platform.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca(2+) signals, release reaction, and a(IIb)beta(3) integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent a(IIb)beta(3) activation by agonists. Thiosulfinates increased the basal intracellular Ca(2+) level of platelets. In activated platelets, they markedly inhibited the Ca(2+) mobilization independently of the external Ca(2+), the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
Sidney W. Whiteheart - One of the best experts on this subject based on the ideXlab platform.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca(2+) signals, release reaction, and a(IIb)beta(3) integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent a(IIb)beta(3) activation by agonists. Thiosulfinates increased the basal intracellular Ca(2+) level of platelets. In activated platelets, they markedly inhibited the Ca(2+) mobilization independently of the external Ca(2+), the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
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Thiosulfinates modulate platelet activation by reaction with surface free Sulfhydryls and internal thiol-containing proteins.
Platelets, 2007Co-Authors: Perrine Badol, Monique David-dufilho, Jacques Auger, Sidney W. Whiteheart, Francine RenduAbstract:Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free Sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free Sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free Sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free Sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with Sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
