The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Hiroyuki Kodama - One of the best experts on this subject based on the ideXlab platform.
-
Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain of D, L-Propargylglycine-treated rats.
Metabolism: clinical and experimental, 2000Co-Authors: Kazunori Sugahara, Kazuko Nakayama, Shiro Awata, Hiroyuki KodamaAbstract:Experimental cystathioninuria was induced in rats by administration of the cystathionine γ-lyase inhibitor, D,L-Propargylglycine. The cystathionine metabolites, cystathionine ketimine (CK) and perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), were identified in whole brain and various regions of the brain in D,L-Propargylglycine-treated rats. The concentration of CK and PHTZDC in whole brain and various regions of the brain increased gradually after administration of D,L-Propargylglycine, and reached the highest value at about 20 hours. CK and PHTZDC accumulated in whole brain and various regions of the brain in proportion to the amount of accumulated cystathionine after D,L-Propargylglycine administration. The concentration of these compounds in the cerebellum was higher versus the other regions of the rat brain.
-
Formation of gamma-glutamylpropargylglycylglycine from Propargylglycine in human blood and erythrocytes.
Acta medica Okayama, 1999Co-Authors: Noboru Nagamine, Hiroyuki Kodama, Jun Ohta, Noriyoshi Masuoka, Toshihiko UbukaAbstract:Gamma-Glutamylpropargylglycylglycine (gamma-Glu-PPG-Gly) was isolated as a metabolite of Propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) from human blood incubated with D,L-Propargylglycine in the presence of L-glutamate and glycine, and identified by fast-atom-bombardment mass spectrometry, indicating that human blood can metabolize Propargylglycine to gamma-Glu-PPG-Gly. When whole blood was incubated with 2 mM D,L-Propargylglycine in the presence of 10 mM L-glutamate and 10 mM glycine at 37 degrees C for 16h, 0.094+/-0.013 micromol of gamma-Glu-PPG-Gly was formed per ml of whole blood. When erythrocytes were incubated under the same conditions for 16h, 0.323+/-0.060 micromol of gamma-Glu-PPG-Gly was formed per ml of erythrocytes, suggesting a large contribution of erythrocytes to gamma-Glu-PPG-Gly formation in whole blood. The apparent Km value of gamma-Glu-PPG-Gly formation in human erythrocytes for D,L-Propargylglycine was 0.32 mM. The observed rate of gamma-Glu-PPG-Gly formation and the Km value for D,L-Propargylglycine suggest that metabolism of Propargylglycine to gamma-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with Propargylglycine.
-
Metabolism of cystathionine, N-monoacetylcystathione, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of d,l-Propargylglycine-treated rats
Metabolism: clinical and experimental, 1998Co-Authors: Jianying Zhang, Kazunori Sugahara, Meiying Zhang, Hiroyuki KodamaAbstract:Abstract Experimental cystathioninuria was induced by injection of d,l -Propargylglycine in rats. The novel cystathionine metabolites, N -monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and d,l -Propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of d,l -Propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of d,l -Propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after d,l -Propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.
-
A new metabolite of Propargylglycine, γ-glutamylpropargylglycylglycine, in liver of d,l-Propargylglycine-administered rats
Biochimica et Biophysica Acta, 1997Co-Authors: Jun Ohta, Kazunori Sugahara, Hiroyuki Kodama, Toshihiko Ubuka, Noboru NagamineAbstract:A new metabolite of Propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) was isolated from liver of rats intraperitoneally administered D,L-Propargylglycine with ion-exchange chromatography, and identified as a glutathione analogue, N-[N-gamma-glutamyl(propargylglycyl)]glycine (gamma-Glu-PPG-Gly), by fast-atom-bombardment-mass spectrometry and reactions of the compound including acid hydrolysis, carboxypeptidase reaction, and gamma-glutamyltranspeptidase reaction. The content of gamma-Glu-PPG-Gly in rat liver increased dose-dependently with the increase of D,L-Propargylglycine. When the dose of D,L-Propargylglycine was 50 mg/kg of body weight, the increase of gamma-Glu-PPG-Gly was proportional to the time after the administration of D,L-Propargylglycine, up to 8 h, and then gradually decreased to about 50% of the maximum at 24 h, where the maximum level of gamma-Glu-PPG-Gly at 8 h was 1.15 +/- 0.08 micromol/g of liver. The Propargylglycine moiety of gamma-Glu-PPG-Gly in rat liver at 14 h after the administration of D,L-Propargylglycine corresponded to 2-7% of the Propargylglycine administered when the dose of D,L-Propargylglycine was 3.125-200 mg/kg of body weight. The present results indicate that gamma-Glu-PPG-Gly is a major intermediate of Propargylglycine metabolism in rat liver. The structural resemblance between glutathione and gamma-Glu-PPG-Gly suggests a possible involvement of Propargylglycine and gamma-Glu-PPG-Gly as cysteine and glutathione analogues, respectively, in sulfur amino-acid metabolism.
-
Identification of perhydro-1,4-thiazepine-3,5-dicarboxylic acid, cystathionine mono-oxo acids, cystathionine ketimines, cystathionine sulfoxide and N-acetylcystathionine sulfoxide in the urine sample of D,L-Propargylglycine treated rats.
Physiological chemistry and physics and medical NMR, 1995Co-Authors: Machida Y, Toshihiko Ubuka, Jianying Zhang, Hashimoto K, H. Wakiguchi, T. Kurashige, Masuoka N, Hiroyuki KodamaAbstract:Novel cystathionine metabolites, perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), cystathionine mono-oxo acids [S-(3-oxo-3-carboxy-n-propyl)cysteine and S-(2-oxo-2-carboxyethyl)homocysteine], cystathionine ketimines, cystathionine sulfoxide and N-acetylcystathionine sulfoxide were identified previously in the urine of patients with cystathioninuria. We have identified these compounds for the first time in the urine of D,L-Propargylglycine-treated rats using LC/APCl-MS (liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system) and an amino acid analyzer. Cystathionine mono-oxo acids and cystathionine ketimines were easily interconvertible depending on the pH of the solution. The excretion of PHTZDC, total cystathionine ketimine (cystathionine mono-oxo acids plus cystathionine ketimines), cystathionine sulfoxide and Nac-cystathionine sulfoxide in the rat urine increased in proportion to that of cystathionine content after D,L-Propargylglycine administration.
Kazunori Sugahara - One of the best experts on this subject based on the ideXlab platform.
-
Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain of D, L-Propargylglycine-treated rats.
Metabolism: clinical and experimental, 2000Co-Authors: Kazunori Sugahara, Kazuko Nakayama, Shiro Awata, Hiroyuki KodamaAbstract:Experimental cystathioninuria was induced in rats by administration of the cystathionine γ-lyase inhibitor, D,L-Propargylglycine. The cystathionine metabolites, cystathionine ketimine (CK) and perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), were identified in whole brain and various regions of the brain in D,L-Propargylglycine-treated rats. The concentration of CK and PHTZDC in whole brain and various regions of the brain increased gradually after administration of D,L-Propargylglycine, and reached the highest value at about 20 hours. CK and PHTZDC accumulated in whole brain and various regions of the brain in proportion to the amount of accumulated cystathionine after D,L-Propargylglycine administration. The concentration of these compounds in the cerebellum was higher versus the other regions of the rat brain.
-
Metabolism of cystathionine, N-monoacetylcystathione, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of d,l-Propargylglycine-treated rats
Metabolism: clinical and experimental, 1998Co-Authors: Jianying Zhang, Kazunori Sugahara, Meiying Zhang, Hiroyuki KodamaAbstract:Abstract Experimental cystathioninuria was induced by injection of d,l -Propargylglycine in rats. The novel cystathionine metabolites, N -monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and d,l -Propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of d,l -Propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of d,l -Propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after d,l -Propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.
-
A new metabolite of Propargylglycine, γ-glutamylpropargylglycylglycine, in liver of d,l-Propargylglycine-administered rats
Biochimica et Biophysica Acta, 1997Co-Authors: Jun Ohta, Kazunori Sugahara, Hiroyuki Kodama, Toshihiko Ubuka, Noboru NagamineAbstract:A new metabolite of Propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) was isolated from liver of rats intraperitoneally administered D,L-Propargylglycine with ion-exchange chromatography, and identified as a glutathione analogue, N-[N-gamma-glutamyl(propargylglycyl)]glycine (gamma-Glu-PPG-Gly), by fast-atom-bombardment-mass spectrometry and reactions of the compound including acid hydrolysis, carboxypeptidase reaction, and gamma-glutamyltranspeptidase reaction. The content of gamma-Glu-PPG-Gly in rat liver increased dose-dependently with the increase of D,L-Propargylglycine. When the dose of D,L-Propargylglycine was 50 mg/kg of body weight, the increase of gamma-Glu-PPG-Gly was proportional to the time after the administration of D,L-Propargylglycine, up to 8 h, and then gradually decreased to about 50% of the maximum at 24 h, where the maximum level of gamma-Glu-PPG-Gly at 8 h was 1.15 +/- 0.08 micromol/g of liver. The Propargylglycine moiety of gamma-Glu-PPG-Gly in rat liver at 14 h after the administration of D,L-Propargylglycine corresponded to 2-7% of the Propargylglycine administered when the dose of D,L-Propargylglycine was 3.125-200 mg/kg of body weight. The present results indicate that gamma-Glu-PPG-Gly is a major intermediate of Propargylglycine metabolism in rat liver. The structural resemblance between glutathione and gamma-Glu-PPG-Gly suggests a possible involvement of Propargylglycine and gamma-Glu-PPG-Gly as cysteine and glutathione analogues, respectively, in sulfur amino-acid metabolism.
-
Determination of D,L-Propargylglycine and N-acetylPropargylglycine in urine and several tissues of D,L-Propargylglycine-treated rats using liquid chromatography mass spectrometry
Journal of chromatography. B Biomedical applications, 1994Co-Authors: Zhang Jianying, Kazunori Sugahara, Yumiko Machida, Hiroyuki KodamaAbstract:Abstract An experimental animal model with cystathioninuria was obtained by the injection of d,l -Propargylglycine into rats. The concentrations of d,l -Propargylglycine in urine, several tissues and serum at different times after the injection were measured by liquid chromatography—mass spectrometry. The Propargylglycine accumulated rapidly in several tissues and serum of the rats, and reached its maximum level at about 2 h after the injection. Approximately 21.2% of the administered Propargylglycine was excreted in urine. N-AcetylPropargylglycine was identified as a new metabolite of Propargylglycine in urine. The concentration of Propargylglycine was 100 times that of N-acetylPropargylglycine in urine.
Jianying Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Metabolism of cystathionine, N-monoacetylcystathione, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of d,l-Propargylglycine-treated rats
Metabolism: clinical and experimental, 1998Co-Authors: Jianying Zhang, Kazunori Sugahara, Meiying Zhang, Hiroyuki KodamaAbstract:Abstract Experimental cystathioninuria was induced by injection of d,l -Propargylglycine in rats. The novel cystathionine metabolites, N -monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and d,l -Propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of d,l -Propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of d,l -Propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after d,l -Propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.
-
Identification of perhydro-1,4-thiazepine-3,5-dicarboxylic acid, cystathionine mono-oxo acids, cystathionine ketimines, cystathionine sulfoxide and N-acetylcystathionine sulfoxide in the urine sample of D,L-Propargylglycine treated rats.
Physiological chemistry and physics and medical NMR, 1995Co-Authors: Machida Y, Toshihiko Ubuka, Jianying Zhang, Hashimoto K, H. Wakiguchi, T. Kurashige, Masuoka N, Hiroyuki KodamaAbstract:Novel cystathionine metabolites, perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), cystathionine mono-oxo acids [S-(3-oxo-3-carboxy-n-propyl)cysteine and S-(2-oxo-2-carboxyethyl)homocysteine], cystathionine ketimines, cystathionine sulfoxide and N-acetylcystathionine sulfoxide were identified previously in the urine of patients with cystathioninuria. We have identified these compounds for the first time in the urine of D,L-Propargylglycine-treated rats using LC/APCl-MS (liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system) and an amino acid analyzer. Cystathionine mono-oxo acids and cystathionine ketimines were easily interconvertible depending on the pH of the solution. The excretion of PHTZDC, total cystathionine ketimine (cystathionine mono-oxo acids plus cystathionine ketimines), cystathionine sulfoxide and Nac-cystathionine sulfoxide in the rat urine increased in proportion to that of cystathionine content after D,L-Propargylglycine administration.
Mohammad Kazem Gharib-naseri - One of the best experts on this subject based on the ideXlab platform.
-
Gastric acid induces mucosal H_2S release in rats by upregulating mRNA and protein expression of cystathionine gamma lyase
The Journal of Physiological Sciences, 2015Co-Authors: Seyyed Ali Mard, Akram Ahangarpour, Ali Veisi, Mohammad Kazem Gharib-naseriAbstract:It is well known that hydrogen sulfide (H_2S) protects the gastric mucosa against gastric acid and other noxious stimulants by several mechanisms but until now the effect of gastric acid on H_2S production has not been evaluated. This study was performed to determine the effect of basal and stimulated gastric acid secretion on mRNA and protein expression of cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), and on mucosal release of H_2S in rats. Seventy-two male rats were randomly assigned into 9 groups (8 in each)—control, distention, and pentagastrin-induced gastric acid secretion groups. The effects of 15 % alcohol solution, Propargylglycine (PAG), l -NAME, and pantoprazole were also investigated. Under anesthesia, animals underwent tracheostomy and midline laparotomy. A catheter was inserted into the stomach through the duodenum for gastric washout. At the end of the experiments, the animals were killed and the gastric mucosa was collected to measure H_2S concentration and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR, and expression of their proteins by western blot. Basal and stimulated gastric acid secretion increased mucosal levels of H_2S, and mRNA and protein expression of CSE. Pantoprazole and l -NAME reversed H_2S release and restored protein expression of CSE to the control level. Pantoprazole, but not Propargylglycine, pretreatment inhibited the elevated level of protein expression of eNOS in response to distention-induced gastric acid secretion. Our findings indicated that NO mediated the stimulatory effect of gastric acid on H_2S release and protein expression of CSE.
-
Gastric acid induces mucosal H2S release in rats by upregulating mRNA and protein expression of cystathionine gamma lyase
The journal of physiological sciences : JPS, 2015Co-Authors: Seyyed Ali Mard, Akram Ahangarpour, Ali Veisi, Mohammad Kazem Gharib-naseriAbstract:It is well known that hydrogen sulfide (H2S) protects the gastric mucosa against gastric acid and other noxious stimulants by several mechanisms but until now the effect of gastric acid on H2S production has not been evaluated. This study was performed to determine the effect of basal and stimulated gastric acid secretion on mRNA and protein expression of cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), and on mucosal release of H2S in rats. Seventy-two male rats were randomly assigned into 9 groups (8 in each)—control, distention, and pentagastrin-induced gastric acid secretion groups. The effects of 15 % alcohol solution, Propargylglycine (PAG), l-NAME, and pantoprazole were also investigated. Under anesthesia, animals underwent tracheostomy and midline laparotomy. A catheter was inserted into the stomach through the duodenum for gastric washout. At the end of the experiments, the animals were killed and the gastric mucosa was collected to measure H2S concentration and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR, and expression of their proteins by western blot. Basal and stimulated gastric acid secretion increased mucosal levels of H2S, and mRNA and protein expression of CSE. Pantoprazole and l-NAME reversed H2S release and restored protein expression of CSE to the control level. Pantoprazole, but not Propargylglycine, pretreatment inhibited the elevated level of protein expression of eNOS in response to distention-induced gastric acid secretion. Our findings indicated that NO mediated the stimulatory effect of gastric acid on H2S release and protein expression of CSE.
Gethin J. Mcbean - One of the best experts on this subject based on the ideXlab platform.
-
Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-gamma-lyase and upregulation of the transsulfuration pathway in C6 glioma cells
Neurochemistry international, 2010Co-Authors: Sarah Kandil, Lorraine Brennan, Gethin J. McbeanAbstract:Cancer cells have a high demand for cysteine as precursor of the antioxidant, glutathione, that is required to promote cell growth and division. Uptake of cystine by the x(c)(-) cystine-glutamate exchanger provides the majority of cysteine, but a significant percentage may be derived from methionine, via a transsulfuration pathway. Our aim was to evaluate the relative contribution of the exchanger and the transsulfuration pathway to glutathione synthesis in astrocytoma/glioblastoma cells, using the C6 glioma cell line as a model system. Blockade of the x(c)(-) exchanger with the gliotoxins l-alphaaminoadipate or l-beta-N-oxalylamino-l-alanine (400 microM) caused a loss of cellular cysteine and depletion in glutathione to 51% and 54% of control, respectively, after 24 h. Inhibition of the transsulfuration pathway with Propargylglycine (1 mM, 24 h) depleted glutathione to 77% of control. Co-incubation of cells with gliotoxin and Propargylglycine reduced glutathione to 39% of control at 24 h and to 20% at 48 h. Expression of cystathionine-gamma-lyase, the rate-limiting enzyme of the transsulfuration pathway, was significantly increased following incubation of the cells with gliotoxins. Incubation of C6 cells with diethylmaleate for 3 h led to a significant reduction in glutathione (63%), whereas expression of cystathionine-gamma-lyase was increased by 1.5-fold. Re-feeding methionine to diethylmaleate-treated cells incubated in the absence of cystine or methionine resulted in a significant recovery in glutathione that was blocked by Propargylglycine. Co-incubation of C6 cells with diethylmaleate and the JNK-inhibitor, SP600125, abolished the increase in expression of cystathionine-gamma-lyase that had been observed in the presence of diethylmaleate alone. Similar results were obtained with the p38(MAPK) inhibitor, SB203580. It is concluded that glutathione depletion causes a JNK- and p38(MAPK)-mediated increase in expression of cystathionine-gamma-lyase that promotes flux through the transsulfuration pathway to compensate for loss of glutathione in C6 glioma cells.
