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Alban Longchamp - One of the best experts on this subject based on the ideXlab platform.
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short term preoperative protein restriction attenuates vein graft disease via induction of Cystathionine γ lyase
Cardiovascular Research, 2019Co-Authors: Kaspar Trocha, Peter Kip, Ming Tao, Michael R Macarthur, Humberto J Trevinovillarreal, Alban LongchampAbstract:Aims Therapies to prevent vein graft disease, a major problem in cardiovascular and lower extremity bypass surgeries, are currently lacking. Short-term preoperative protein restriction holds promise as an effective preconditioning method against surgical stress in rodent models, but whether it can improve vein graft patency after bypass surgery is undetermined. Here, we hypothesized that short-term protein restriction would limit vein graft disease via up-regulation of Cystathionine γ-lyase and increased endogenous production of the cytoprotective gaseous signalling molecule hydrogen sulfide. Methods and results Low-density lipoprotein receptor knockout mice were preconditioned for 1 week on a high-fat high-cholesterol (HFHC) diet with or without protein prior to left common carotid interposition vein graft surgery with caval veins from donor mice on corresponding diets. Both groups were returned to a complete HFHC diet post-operatively, and vein grafts analysed 4 or 28 days later. A novel global transgenic Cystathionine γ-lyase overexpressing mouse model was also employed to study effects of genetic overexpression on graft patency. Protein restriction decreased vein graft intimal/media+adventitia area and thickness ratios and intimal smooth muscle cell infiltration 28 days post-operatively, and neutrophil transmigration 4 days post-operatively. Protein restriction increased Cystathionine γ-lyase protein expression in aortic and caval vein endothelial cells (ECs) and frequency of lung EC producing hydrogen sulfide. The Cystathionine γ-lyase inhibitor propargylglycine abrogated protein restriction-mediated protection from graft failure and the increase in hydrogen sulfide-producing ECs, while Cystathionine γ-lyase transgenic mice displayed increased hydrogen sulfide production capacity and were protected from vein graft disease independent of diet. Conclusion One week of protein restriction attenuates vein graft disease via increased Cystathionine γ-lyase expression and hydrogen sulfide production, and decreased early inflammation. Dietary or pharmacological interventions to increase Cystathionine γ-lyase or hydrogen sulfide may thus serve as new and practical strategies to improve vein graft durability.
Peter Kip - One of the best experts on this subject based on the ideXlab platform.
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short term preoperative protein restriction attenuates vein graft disease via induction of Cystathionine γ lyase
Cardiovascular Research, 2019Co-Authors: Kaspar Trocha, Peter Kip, Ming Tao, Michael R Macarthur, Humberto J Trevinovillarreal, Alban LongchampAbstract:Aims Therapies to prevent vein graft disease, a major problem in cardiovascular and lower extremity bypass surgeries, are currently lacking. Short-term preoperative protein restriction holds promise as an effective preconditioning method against surgical stress in rodent models, but whether it can improve vein graft patency after bypass surgery is undetermined. Here, we hypothesized that short-term protein restriction would limit vein graft disease via up-regulation of Cystathionine γ-lyase and increased endogenous production of the cytoprotective gaseous signalling molecule hydrogen sulfide. Methods and results Low-density lipoprotein receptor knockout mice were preconditioned for 1 week on a high-fat high-cholesterol (HFHC) diet with or without protein prior to left common carotid interposition vein graft surgery with caval veins from donor mice on corresponding diets. Both groups were returned to a complete HFHC diet post-operatively, and vein grafts analysed 4 or 28 days later. A novel global transgenic Cystathionine γ-lyase overexpressing mouse model was also employed to study effects of genetic overexpression on graft patency. Protein restriction decreased vein graft intimal/media+adventitia area and thickness ratios and intimal smooth muscle cell infiltration 28 days post-operatively, and neutrophil transmigration 4 days post-operatively. Protein restriction increased Cystathionine γ-lyase protein expression in aortic and caval vein endothelial cells (ECs) and frequency of lung EC producing hydrogen sulfide. The Cystathionine γ-lyase inhibitor propargylglycine abrogated protein restriction-mediated protection from graft failure and the increase in hydrogen sulfide-producing ECs, while Cystathionine γ-lyase transgenic mice displayed increased hydrogen sulfide production capacity and were protected from vein graft disease independent of diet. Conclusion One week of protein restriction attenuates vein graft disease via increased Cystathionine γ-lyase expression and hydrogen sulfide production, and decreased early inflammation. Dietary or pharmacological interventions to increase Cystathionine γ-lyase or hydrogen sulfide may thus serve as new and practical strategies to improve vein graft durability.
Kaspar Trocha - One of the best experts on this subject based on the ideXlab platform.
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short term preoperative protein restriction attenuates vein graft disease via induction of Cystathionine γ lyase
Cardiovascular Research, 2019Co-Authors: Kaspar Trocha, Peter Kip, Ming Tao, Michael R Macarthur, Humberto J Trevinovillarreal, Alban LongchampAbstract:Aims Therapies to prevent vein graft disease, a major problem in cardiovascular and lower extremity bypass surgeries, are currently lacking. Short-term preoperative protein restriction holds promise as an effective preconditioning method against surgical stress in rodent models, but whether it can improve vein graft patency after bypass surgery is undetermined. Here, we hypothesized that short-term protein restriction would limit vein graft disease via up-regulation of Cystathionine γ-lyase and increased endogenous production of the cytoprotective gaseous signalling molecule hydrogen sulfide. Methods and results Low-density lipoprotein receptor knockout mice were preconditioned for 1 week on a high-fat high-cholesterol (HFHC) diet with or without protein prior to left common carotid interposition vein graft surgery with caval veins from donor mice on corresponding diets. Both groups were returned to a complete HFHC diet post-operatively, and vein grafts analysed 4 or 28 days later. A novel global transgenic Cystathionine γ-lyase overexpressing mouse model was also employed to study effects of genetic overexpression on graft patency. Protein restriction decreased vein graft intimal/media+adventitia area and thickness ratios and intimal smooth muscle cell infiltration 28 days post-operatively, and neutrophil transmigration 4 days post-operatively. Protein restriction increased Cystathionine γ-lyase protein expression in aortic and caval vein endothelial cells (ECs) and frequency of lung EC producing hydrogen sulfide. The Cystathionine γ-lyase inhibitor propargylglycine abrogated protein restriction-mediated protection from graft failure and the increase in hydrogen sulfide-producing ECs, while Cystathionine γ-lyase transgenic mice displayed increased hydrogen sulfide production capacity and were protected from vein graft disease independent of diet. Conclusion One week of protein restriction attenuates vein graft disease via increased Cystathionine γ-lyase expression and hydrogen sulfide production, and decreased early inflammation. Dietary or pharmacological interventions to increase Cystathionine γ-lyase or hydrogen sulfide may thus serve as new and practical strategies to improve vein graft durability.
H. Kimura - One of the best experts on this subject based on the ideXlab platform.
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the possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide
Biochemical and Biophysical Research Communications, 1997Co-Authors: Rumiko Hosoki, Norio Matsuki, H. KimuraAbstract:Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously in mammalian tissues from L-cysteine mainly by two pyridoxal-5′-phosphate-dependent enzymes, Cystathionine β-synthetase and Cystathionine γ-lyase. Recently, we showed that Cystathionine β-synthetase in the brain produces H2S, and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing NMDA receptor activity. Here we show that mRNA for another H2S producing enzyme, Cystathionine γ-lyase, is expressed in the ileum, portal vein, and thoracic aorta. The ileum also expresses Cystathionine β-synthetase mRNA. These tissues produce H2S, and this production is blocked by Cystathionine β-synthetase and Cystathionine γ-lyase specific inhibitors. Although exogenously applied H2S alone relaxed these smooth muscles, much lower concentrations of H2S greatly enhanced the smooth muscle relaxation induced by NO in the thoracic aorta. These observations suggest that the endogenous H2S may regulate smooth muscle tone in synergy with NO.
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The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide.
Biochemical and biophysical research communications, 1997Co-Authors: Rumiko Hosoki, Norio Matsuki, H. KimuraAbstract:Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously in mammalian tissues from L-cysteine mainly by two pyridoxal-5'-phosphate-dependent enzymes, Cystathionine beta-synthetase and Cystathionine gamma-lyase. Recently, we showed that Cystathionine beta-synthetase in the brain produces H2S, and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing NMDA receptor activity. Here we show that mRNA for another H2S producing enzyme, Cystathionine gamma-lyase, is expressed in the ileum, portal vein, and thoracic aorta. The ileum also expresses Cystathionine beta-synthetase mRNA. These tissues produce H2S, and this production is blocked by Cystathionine beta-synthetase and Cystathionine gamma-lyase specific inhibitors. Although exogenously applied H2S alone relaxed these smooth muscles, much lower concentrations of H2S greatly enhanced the smooth muscle relaxation induced by NO in the thoracic aorta. These observations suggest that the endogenous H2S may regulate smooth muscle tone in synergy with NO.
Edith Wilson Miles - One of the best experts on this subject based on the ideXlab platform.
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yeast Cystathionine beta synthase reacts with l allothreonine a non natural substrate and l homocysteine to form a new amino acid 3 methyl l Cystathionine
Biochemistry, 2002Co-Authors: Kwanghwan Jhee, Peter Mcphie, Dimitri Niks, Michael F Dunn, Edith Wilson MilesAbstract:Our studies of the reaction mechanism of Cystathionine beta-synthase from yeast (Saccharomyces cerevisiae) are facilitated by the spectroscopic properties of the pyridoxal phosphate coenzyme. The enzyme catalyzes the reaction of L-serine with L-homocysteine to form L-Cystathionine through a series of pyridoxal phosphate intermediates. In this work, we explore the substrate specificity of the enzyme by use of substrate analogues combined with kinetic measurements under pre-steady-state conditions and with circular dichroism and fluorescence spectroscopy under steady-state conditions. Our results show that L-allothreonine, but not L-threonine, serves as an effective substrate. L-Allothreonine reacts with the pyridoxal phosphate cofactor to form a stable 3-methyl aminoacrylate intermediate that absorbs maximally at 446 nm. The rapid-scanning stopped-flow results show that the binding of L-allothreonine as the external aldimine is faster than formation of the 3-methyl aminoacrylate intermediate. The 3-methyl aminoacrylate intermediate reacts with L-homocysteine to form a new amino acid, 3-methyl-L-Cystathionine, which was characterized by nuclear magnetic resonance spectroscopy. This new amino acid may be a useful analogue of L-Cystathionine.
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yeast Cystathionine β synthase is a pyridoxal phosphate enzyme but unlike the human enzyme is not a heme protein
Journal of Biological Chemistry, 2000Co-Authors: Kwanghwan Jhee, Peter Mcphie, Edith Wilson MilesAbstract:Abstract Our studies of Cystathionine β-synthase fromSaccharomyces cerevisiae (yeast) are aimed at (1) clarifying the cofactor dependence and catalytic mechanism and (2) obtaining a system for future investigations of the effects of mutations that cause human disease (homocystinuria or coronary heart disease). We report methods that yielded high expression of the yeast gene in Escherichia coli and of purified yeast Cystathionine β-synthase. The absorption and circular dichroism spectra of the homogeneous enzyme were characteristic of a pyridoxal phosphate enzyme and showed the absence of heme, which is found in human and rat Cystathionine β-synthase. The absence of heme in the yeast enzyme facilitates spectroscopic studies to probe the catalytic mechanism. The reaction of the enzyme with l-serine in the absence of l-homocysteine produced the aldimine of aminoacrylate, which absorbed at 460 nm and had a strong negative circular dichroism band at 460 nm. The formation of this intermediate from the product, l-Cystathionine, demonstrates the partial reversibility of the reaction. Our results establish the overall catalytic mechanism of yeast Cystathionine β-synthase and provide a useful system for future studies of structure and function. The absence of heme in the functional yeast enzyme suggests that heme does not play an essential catalytic role in the rat and human enzymes. The results are consistent with the absence of heme in the closely related enzymesO-acetylserine sulfhydrylase, threonine deaminase, and tryptophan synthase.
