|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 45, 42912-42918, November 8, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Homocysteine metabolism is altered in diabetic
patients. Cystathionine
Hormonal Regulation of Cystathionine
-Synthase Expression
in Liver*
§,
,,**
Department of Biochemistry, Memorial
University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada
and the ¶ Department of Pediatrics, University of Colorado School
of Medicine, Denver, Colorado 80262
-synthase (CBS), a key enzyme involved in
the transsulfuration pathway, which irreversibly converts homocysteine
to cysteine, catalyzes the condensation of serine and homocysteine to
cystathionine. Studies in streptozotocin-induced diabetic rats have
shown that CBS enzyme activity is elevated in the liver but not in the
kidney, and this effect is reversed by insulin treatment. To determine whether these effects resulted from alterations at the level of gene
transcription, CBS mRNA was measured in diabetic and
insulin-treated diabetic rats. CBS mRNA levels were found to be
markedly higher in streptozotocin-induced diabetic rat livers; these
were reduced by insulin administration. In H4IIE cells, a rat hepatoma
cell culture model, glucocorticoids increased the cellular levels of CBS enzyme protein and CBS mRNA; insulin inhibited this stimulatory effect. Treatment with insulin also decreased CBS levels in HepG2 cells, a human hepatoma cell line. Nuclear run-on experiments in the
rat cells confirmed that stimulation of CBS gene expression by
glucocorticoids and the inhibition by insulin occurred at the transcriptional level. Transient transfections of HepG2 cells with a
CBS-1b promoter luciferase reporter construct showed that the promoter
activity was decreased by 70% after insulin treatment. These results
show that insulin has a direct role in regulating homocysteine
metabolism. Altered insulin levels in diseases such as diabetes may
influence homocysteine metabolism by regulating the hepatic
transsulfuration pathway.
*
This work was supported by the Margaret L. Webb grant from
the Canadian Diabetes Association (CDA) (to J. T. B. and M. E. B.),
grants from the Canadian Institutes of Health Research (CIHR) (to
J. T. B., M. E. B., and J. T. B.), and National Institutes of
Health Grant P01HD805 (to J. P. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a CIHR doctoral award.
**
To whom correspondence should be addressed: Dept. of Biochemistry,
Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9,
Canada. Tel.: 709-737-8540/8543; Fax: 709-737-2422; E-mail: jbrosnan@mun.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E.-P. I. Chiang, Y.-C. Wang, W.-W. Chen, and F.-Y. Tang Effects of Insulin and Glucose on Cellular Metabolic Fluxes in Homocysteine Transsulfuration, Remethylation, S-Adenosylmethionine Synthesis, and Global Deoxyribonucleic Acid Methylation J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 1017 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lamers, J. Williamson, M. Ralat, E. P. Quinlivan, L. R. Gilbert, C. Keeling, R. D. Stevens, C. B. Newgard, P. M. Ueland, K. Meyer, et al. Moderate Dietary Vitamin B-6 Restriction Raises Plasma Glycine and Cystathionine Concentrations While Minimally Affecting the Rates of Glycine Turnover and Glycine Cleavage in Healthy Men and Women J. Nutr., March 1, 2009; 139(3): 452 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Williams, T. A. Garrow, and K. L. Schalinske Type I Diabetes Leads to Tissue-Specific DNA Hypomethylation in Male Rats J. Nutr., November 1, 2008; 138(11): 2064 - 2069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yang, W. Yang, L. Wu, and R. Wang H2S, Endoplasmic Reticulum Stress, and Apoptosis of Insulin-secreting Beta Cells J. Biol. Chem., June 1, 2007; 282(22): 16567 - 16576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Hartz, K. M. Nieman, R. L. Jacobs, D. E. Vance, and K. L. Schalinske Hepatic Phosphatidylethanolamine N-Methyltransferase Expression Is Increased in Diabetic Rats J. Nutr., December 1, 2006; 136(12): 3005 - 3009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Nieman, C. S. Hartz, S. S. Szegedi, T. A. Garrow, J. D. Sparks, and K. L. Schalinske Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1235 - E1242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Guzman, M. A. Navarro, R. Carnicer, A. J. Sarria, S. Acin, C. Arnal, P. Muniesa, J. C. Surra, J. M. Arbones-Mainar, N. Maeda, et al. Cystathionine {beta}-synthase is essential for female reproductive function Hum. Mol. Genet., November 1, 2006; 15(21): 3168 - 3176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Abu-Lebdeh, R. Barazzoni, S. E. Meek, M. L. Bigelow, X.-M. T. Persson, and K. S. Nair Effects of Insulin Deprivation and Treatment on Homocysteine Metabolism in People with Type 1 Diabetes J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3344 - 3348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Kullo, K. Ding, E. Boerwinkle, S. T. Turner, T. H. Mosley Jr, S. L.R. Kardia, and M. de Andrade Novel Genomic Loci Influencing Plasma Homocysteine Levels Stroke, July 1, 2006; 37(7): 1703 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ingenbleek The Nutritional Relationship Linking Sulfur to Nitrogen in Living Organisms J. Nutr., June 1, 2006; 136(6): 1641S - 1651S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ratnam, E. P. Wijekoon, B. Hall, T. A. Garrow, M. E. Brosnan, and J. T. Brosnan Effects of diabetes and insulin on betaine-homocysteine S-methyltransferase expression in rat liver Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E933 - E939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H. Cho, S. Lim, H. C. Jang, H. K. Park, and B. E. Metzger Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus: A 4-year prospective study Diabetes Care, November 1, 2005; 28(11): 2750 - 2755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Wijekoon, B. Hall, S. Ratnam, M. E. Brosnan, S. H. Zeisel, and J. T. Brosnan Homocysteine Metabolism in ZDF (Type 2) Diabetic Rats Diabetes, November 1, 2005; 54(11): 3245 - 3251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tessari, A. Coracina, E. Kiwanuka, M. Vedovato, M. Vettore, A. Valerio, M. Zaramella, and G. Garibotto Effects of Insulin on Methionine and Homocysteine Kinetics in Type 2 Diabetes With Nephropathy Diabetes, October 1, 2005; 54(10): 2968 - 2976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tessari, E. Kiwanuka, A. Coracina, M. Zaramella, M. Vettore, A. Valerio, and G. Garibotto Insulin in methionine and homocysteine kinetics in healthy humans: plasma vs. intracellular models Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1270 - E1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Ulrey, L. Liu, L. G. Andrews, and T. O. Tollefsbol The impact of metabolism on DNA methylation Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R139 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Papoutsakis, N. Yiannakouris, Y. Manios, E. Papaconstantinou, F. Magkos, K. H. Schulpis, A. Zampelas, and A. L. Matalas Plasma Homocysteine Concentrations in Greek Children Are Influenced by an Interaction between the Methylenetetrahydrofolate Reductase C677T Genotype and Folate Status J. Nutr., March 1, 2005; 135(3): 383 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mukudai, S. Kubota, T. Eguchi, S. Kondo, K. Nakao, and M. Takigawa Regulation of Chicken ccn2 Gene by Interaction between RNA cis-Element and Putative trans-Factor during Differentiation of Chondrocytes J. Biol. Chem., February 4, 2005; 280(5): 3166 - 3177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Nieman, M. J. Rowling, T. A. Garrow, and K. L. Schalinske Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid J. Biol. Chem., October 29, 2004; 279(44): 45708 - 45712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kim, K. J. Woodcroft, S. S. Khodadadeh, and R. F. Novak Insulin Signaling Regulates {gamma}-Glutamylcysteine Ligase Catalytic Subunit Expression in Primary Cultured Rat Hepatocytes J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kohli, C. J. Meininger, T. E. Haynes, W. Yan, J. T. Self, and G. Wu Dietary L-Arginine Supplementation Enhances Endothelial Nitric Oxide Synthesis in Streptozotocin-Induced Diabetic Rats J. Nutr., March 1, 2004; 134(3): 600 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Rowling and K. L. Schalinske Retinoic Acid and Glucocorticoid Treatment Induce Hepatic Glycine N-Methyltransferase and Lower Plasma Homocysteine Concentrations in Rats and Rat Hepatoma Cells J. Nutr., November 1, 2003; 133(11): 3392 - 3398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-G. Zou and R. Banerjee Tumor Necrosis Factor-alpha -induced Targeted Proteolysis of Cystathionine beta -Synthase Modulates Redox Homeostasis J. Biol. Chem., May 2, 2003; 278(19): 16802 - 16808. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |