The Experts below are selected from a list of 120 Experts worldwide ranked by ideXlab platform
Takeyori Saheki - One of the best experts on this subject based on the ideXlab platform.
-
Antagonizing effect of AP-1 on glucocorticoid induction of Urea Cycle Enzymes: a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice.
Molecular genetics and metabolism, 2000Co-Authors: Takeyori Saheki, Keiko KobayashiAbstract:Hyperammonemia is one of the major symptoms of primary carnitine deficiency. Carnitine-deficient juvenile visceral steatosis (JVS) mice show hyperammonemia during the weaning period. We have found that all of the Urea Cycle enzyme genes are suppressed and that N-acetylglutamate, an allosteric activator of the first step enzyme of the Urea Cycle, carbamoyl phosphate synthetase I (CPS), is not deficient in the liver of JVS mice. Induction of the Urea Cycle Enzymes by glucocorticoid in rat primary cultured hepatocytes was suppressed by the addition of long-chain fatty acids. The suppression of the Urea Cycle enzyme genes in vivo and in vitro is accompanied by stimulated AP-1 DNA-binding activity. However, mRNA of phosphoenolpyruvate carboxykinase, one of the gluconeogenic Enzymes which responds to glucocorticoid, is further stimulated by the addition of fatty acid. From these results, we postulate that protein-protein interaction between glucocorticoid receptors and AP-1 is not the major mechanism of suppression, but that AP-1 causes the suppression through a cis-element on the gene. After cloning promoter and enhancer regions of the mouse CPS gene and comparing rat and mouse, we found that an AP-1 site was present just 3'-downstream of the minimal essential enhancer fragment previously described. We also found that the presence of an AP-1 site in reporter gene constructs resulted in suppression of the reporter genes in the liver of carnitine-deficient JVS mice and suppression of glucocorticoid induction by long-chain fatty acid in cultured hepatocytes.
-
Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of Urea Cycle Enzymes by normalizing their transcription.
The Journal of biological chemistry, 1992Co-Authors: Masahisa Horiuchi, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Keiko Kobayashi, Mineko Tomomura, Masamichi Kuwajima, Takeyori SahekiAbstract:Abstract Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of Urea Cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two Urea Cycle Enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of Enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of Urea Cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
-
Abnormal expression of Urea Cycle enzyme genes in juvenile visceral steatosis (jvs) mice.
Biochimica et biophysica acta, 1992Co-Authors: Mineko Tomomura, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Masahisa Horiuchi, Takeyori SahekiAbstract:Abstract Juvenile visceral steatosis (jvs) mice from the C3H-H-2° strain have markedly low levels of all the hepatic Urea Cycle Enzymes (Imamura et al. (1990) FEBS Lett. 260, 119–121). The steady state levels of messenger RNA for the four Urea Cycle Enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific Enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the Urea Cycle Enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the Urea Cycle Enzymes but also the regulation of their developmental induction.
Patricia A. Wright - One of the best experts on this subject based on the ideXlab platform.
-
Effects of exercise on nitrogen excretion, carbamoyl phosphate synthetase III activity and related Urea Cycle Enzymes in muscle and liver tissues of juvenile rainbow trout (Oncorhynchus mykiss).
Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2001Co-Authors: A E Todgham, P M Anderson, Patricia A. WrightAbstract:The purpose of this study was to determine if carbamoyl phosphate synthetase III (CPSase III) and related Urea Cycle enzyme activities in skeletal muscle tissue of juvenile rainbow trout (Oncorhynchus mykiss) increase during short- or long-term exercise, in parallel with changes in whole-body Urea excretion rates. Urea excretion was elevated by 65% in fish that swam at high-speed (50 cm/s) vs. low-speed (20 cm/s) over a 2-h period, with no significant changes in CPSase III, ornithine transcarbamoylase or glutamine synthetase activities in muscle tissue. Fish that swam for 4 days at high-speed had higher rates of ammonia excretion and GSase activity in muscle and liver tissue relative to low-speed swimmers. Calculations showed that 47-53% of excreted Urea, theoretically could be accounted for by total muscle CPSase III activity in juvenile and adult trout. The data indicate that increases in the rate of Urea excretion during short-term high intensity exercise are not linked to higher activities of Urea Cycle Enzymes in muscle tissue, but this does not rule out the possibility of increased flux through muscle CPSase III and related Enzymes. Furthermore, these results indicate that Urea Cycle enzyme activities in skeletal muscle tissue can account for a significant portion of total Urea excretion in juvenile and adult trout.
-
Expression and Activity of Carbamoyl Phosphate Synthetase III and Ornithine Urea Cycle Enzymes in Various Tissues of Four Fish Species
Comparative Biochemistry and Physiology B, 1998Co-Authors: Andrew K. Felskie, Paul M. Anderson, Patricia A. WrightAbstract:Abstract Previous studies have reported low activities of carbamoyl phosphate synthetase (CPSase) and other ornithine Urea Cycle Enzymes in the liver of many teleost fishes, but it was not established if the CPSase was the Urea Cycle-related CPSase III or pyrimidine pathway-related CPSase II. The purpose of this study was to investigate the expression of the Urea Cycle-related CPSase III and other ornithine Urea Cycle Enzymes in the liver, muscle, intestine, and kidney of three adult teleost fish (common carp, Cyprinus carpio ; goldfish, Carassius auratus ; channel catfish, Ictalurus punctatus ) and a holostean fish (bowfin, Amia calva ). In contrast to previous literature reports, CPSase III activity was absent from the liver of all fish studied. Surprisingly, CPSase III was present in the muscle of the common carp and bowfin and in the intestine of bowfin. Variable levels of the remaining Urea Cycle Enzymes, as well as the pyrimidine nucleotide pathway-related CPSase II were expressed by all tissues and fish examined. We conclude that hepatic CPSase III expression may be relatively rare in teleost and holostean fishes, but expression in extrahepatic tissues, particularly muscle, may be more typical.
Keiko Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
Antagonizing effect of AP-1 on glucocorticoid induction of Urea Cycle Enzymes: a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice.
Molecular genetics and metabolism, 2000Co-Authors: Takeyori Saheki, Keiko KobayashiAbstract:Hyperammonemia is one of the major symptoms of primary carnitine deficiency. Carnitine-deficient juvenile visceral steatosis (JVS) mice show hyperammonemia during the weaning period. We have found that all of the Urea Cycle enzyme genes are suppressed and that N-acetylglutamate, an allosteric activator of the first step enzyme of the Urea Cycle, carbamoyl phosphate synthetase I (CPS), is not deficient in the liver of JVS mice. Induction of the Urea Cycle Enzymes by glucocorticoid in rat primary cultured hepatocytes was suppressed by the addition of long-chain fatty acids. The suppression of the Urea Cycle enzyme genes in vivo and in vitro is accompanied by stimulated AP-1 DNA-binding activity. However, mRNA of phosphoenolpyruvate carboxykinase, one of the gluconeogenic Enzymes which responds to glucocorticoid, is further stimulated by the addition of fatty acid. From these results, we postulate that protein-protein interaction between glucocorticoid receptors and AP-1 is not the major mechanism of suppression, but that AP-1 causes the suppression through a cis-element on the gene. After cloning promoter and enhancer regions of the mouse CPS gene and comparing rat and mouse, we found that an AP-1 site was present just 3'-downstream of the minimal essential enhancer fragment previously described. We also found that the presence of an AP-1 site in reporter gene constructs resulted in suppression of the reporter genes in the liver of carnitine-deficient JVS mice and suppression of glucocorticoid induction by long-chain fatty acid in cultured hepatocytes.
-
Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of Urea Cycle Enzymes by normalizing their transcription.
The Journal of biological chemistry, 1992Co-Authors: Masahisa Horiuchi, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Keiko Kobayashi, Mineko Tomomura, Masamichi Kuwajima, Takeyori SahekiAbstract:Abstract Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of Urea Cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two Urea Cycle Enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of Enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of Urea Cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
Masahisa Horiuchi - One of the best experts on this subject based on the ideXlab platform.
-
Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of Urea Cycle Enzymes by normalizing their transcription.
The Journal of biological chemistry, 1992Co-Authors: Masahisa Horiuchi, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Keiko Kobayashi, Mineko Tomomura, Masamichi Kuwajima, Takeyori SahekiAbstract:Abstract Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of Urea Cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two Urea Cycle Enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of Enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of Urea Cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
-
Abnormal expression of Urea Cycle enzyme genes in juvenile visceral steatosis (jvs) mice.
Biochimica et biophysica acta, 1992Co-Authors: Mineko Tomomura, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Masahisa Horiuchi, Takeyori SahekiAbstract:Abstract Juvenile visceral steatosis (jvs) mice from the C3H-H-2° strain have markedly low levels of all the hepatic Urea Cycle Enzymes (Imamura et al. (1990) FEBS Lett. 260, 119–121). The steady state levels of messenger RNA for the four Urea Cycle Enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific Enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the Urea Cycle Enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the Urea Cycle Enzymes but also the regulation of their developmental induction.
Mineko Tomomura - One of the best experts on this subject based on the ideXlab platform.
-
Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of Urea Cycle Enzymes by normalizing their transcription.
The Journal of biological chemistry, 1992Co-Authors: Masahisa Horiuchi, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Keiko Kobayashi, Mineko Tomomura, Masamichi Kuwajima, Takeyori SahekiAbstract:Abstract Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of Urea Cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two Urea Cycle Enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of Enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of Urea Cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
-
Abnormal expression of Urea Cycle enzyme genes in juvenile visceral steatosis (jvs) mice.
Biochimica et biophysica acta, 1992Co-Authors: Mineko Tomomura, Yasushi Imamura, Tsutomu Koizumi, Hiroko Nikaido, Jun-ichiro Hayakawa, Masahisa Horiuchi, Takeyori SahekiAbstract:Abstract Juvenile visceral steatosis (jvs) mice from the C3H-H-2° strain have markedly low levels of all the hepatic Urea Cycle Enzymes (Imamura et al. (1990) FEBS Lett. 260, 119–121). The steady state levels of messenger RNA for the four Urea Cycle Enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific Enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the Urea Cycle Enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the Urea Cycle Enzymes but also the regulation of their developmental induction.
