Volume 271, Number 25, Issue of June 21, 1996 pp. 15146-15152
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Long Exposure to High Glucose Concentration Impairs the Responsive Expression of -Glutamylcysteine Synthetase by Interleukin-1 and Tumor Necrosis Factor- in Mouse Endothelial Cells

(Received for publication, September 25, 1995, and in revised form, March 19, 1996)

Yoshishige Urata , Hidefumi Yamamoto ^§ , Shinji Goto , Hideki Tsushima ^§ , Shouichi Akazawa ^§ , Shunichi Yamashita ^¶ , Shigenobu Nagataki ^§ and Takahito Kondo

From the  Department of Pathological Biochemistry, the ^¶ Department of Cellular Physiology, Atomic Disease Institute, and the ^§ First Department of Medicine, Nagasaki University School of Medicine, Nagasaki 852, Japan

To elucidate the pathological metabolism of glutathione synthesis in diabetic endothelial cells, we studied the expression of -glutamylcysteine synthetase (-GCS) using a mouse vascular endothelial cell line.

Exposing normoglycemic endothelial cells to tumor necrosis factor- (TNF-) or interleukin-1 (IL-1) increased the activity and the mRNA expression of -GCS. The addition of inhibitors for nuclear factor B (NF-B) to the cells caused a loss of the -GCS mRNA expression in response to TNF-.

A shift of the concentration of glucose in the medium from 5.5 to 28 mM glucose and a following incubation for 7 days decreased the expression of -GCS mRNA. These cells showed no apparent responses of -GCS mRNA or the activity of NF-B to TNF- or IL-. Increase in the GSH concentration of the cells treated with 28 mM glucose restored the expression of -GCS mRNA and its response to TNF- or IL-, suggesting that redox regulation is involved in the expression of -GCS.

In summary, the expression of -GCS is regulated by TNF- or IL-1 in endothelial cells mediated by NF-B stimulation, and impairment of the regulation of -GCS in hyperglycemic cells may be a cause of medical complications that develop in diabetes mellitus.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Glyn-Jones, S. Song, M. A. Black, A. R. J. Phillips, S. Y. Choong, and G. J. S. Cooper Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease Physiol Genomics, February 12, 2007; 28(3): 284 - 293. [Abstract] [Full Text] [PDF]

				P. O. T. Tran, S. M. Parker, E. LeRoy, C. C. Franklin, T. J. Kavanagh, T. Zhang, H. Zhou, P. Vliet, E. Oseid, J. S. Harmon, et al. Adenoviral Overexpression of the Glutamylcysteine Ligase Catalytic Subunit Protects Pancreatic Islets against Oxidative Stress J. Biol. Chem., December 24, 2004; 279(52): 53988 - 53993. [Abstract] [Full Text] [PDF]

				R A Kowluru and S Odenbach Role of interleukin-1{beta} in the pathogenesis of diabetic retinopathy Br. J. Ophthalmol., October 1, 2004; 88(10): 1343 - 1347. [Abstract] [Full Text] [PDF]

				V. Vitvitsky, S. Dayal, S. Stabler, Y. Zhou, H. Wang, S. R. Lentz, and R. Banerjee Perturbations in homocysteine-linked redox homeostasis in a murine model for hyperhomocysteinemia Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R39 - R46. [Abstract] [Full Text] [PDF]

				D. A. DICKINSON and H. J. FORMAN Glutathione in Defense and Signaling: Lessons from a Small Thiol Ann. N.Y. Acad. Sci., November 1, 2002; 973(1): 488 - 504. [Abstract] [Full Text] [PDF]

				Y. Tanaka, P. O. T. Tran, J. Harmon, and R. P. Robertson A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity PNAS, September 17, 2002; 99(19): 12363 - 12368. [Abstract] [Full Text] [PDF]

				S. GOTO, Y. IHARA, Y. URATA, S. IZUMI, K. ABE, T. KOJI, and T. KONDO Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase {pi} FASEB J, December 1, 2001; 15(14): 2702 - 2714. [Abstract] [Full Text] [PDF]

				C. E. Gleason, M. Gonzalez, J. S. Harmon, and R. P. Robertson Determinants of glucose toxicity and its reversibility in the pancreatic islet beta -cell line, HIT-T15 Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E997 - E1002. [Abstract] [Full Text] [PDF]

				F. PUSKAS, P. GERGELY JR, K. BANKI, and A. PERL Stimulation of the pentose phosphate pathway and glutathione levels by dehydroascorbate, the oxidized form of vitamin C FASEB J, July 1, 2000; 14(10): 1352 - 1361. [Abstract] [Full Text]

				H. Amano, H. Yamamoto, M. Senba, K. Oishi, S. Suzuki, K. Fukushima, N. Mukaida, K. Matsushima, K. Eguchi, and T. Nagatake Impairment of Endotoxin-Induced Macrophage Inflammatory Protein 2 Gene Expression in Alveolar Macrophages in Streptozotocin-Induced Diabetes in Mice Infect. Immun., May 1, 2000; 68(5): 2925 - 2929. [Abstract] [Full Text] [PDF]

				I. Rahman and W. MacNee Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1067 - L1088. [Abstract] [Full Text] [PDF]

				S. C. Lu, Y. Bao, Z.-Z. Huang, V. P. Sarthy, and R. Kannan Regulation of {gamma}-Glutamylcysteine Synthetase Subunit Gene Expression in Retinal Muller Cells by Oxidative Stress Invest. Ophthalmol. Vis. Sci., July 1, 1999; 40(8): 1776 - 1782. [Abstract] [Full Text] [PDF]

				S. C. LU Regulation of hepatic glutathione synthesis: current concepts and controversies FASEB J, July 1, 1999; 13(10): 1169 - 1183. [Abstract] [Full Text]

				I. Rahman, F. Antonicelli, and W. MacNee Molecular Mechanism of the Regulation of Glutathione Synthesis by Tumor Necrosis Factor-alpha and Dexamethasone in Human Alveolar Epithelial Cells J. Biol. Chem., February 19, 1999; 274(8): 5088 - 5096. [Abstract] [Full Text] [PDF]

				R.-M. Liu, L. Gao, J. Choi, and H. J. Forman gamma -Glutamylcysteine synthetase: mRNA stabilization and independent subunit transcription by 4-hydroxy-2-nonenal Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L861 - L869. [Abstract] [Full Text] [PDF]