© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
High-glucose-induced nuclear factor
B activation in vascular smooth muscle cells
Department of Endocrinology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
* Corresponding author. Tel.: +81-282-87-2150; fax: +81-282-86-4632
Objective: Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy. This dysfunction may be caused or exacerbated by expression of many of genes potently activated by the transcriptional factor nuclear factor
B (NF-
B). We have examined whether culture of VSMCs under high glucose conditions to stimulate the diabetic state can lead to the activation of NF-
B. Methods: NF-
B activation was assessed in VSMCs stably transfected with a cis-reporter plasmid containing the NF-
B binding sites. Results: Within 3-h incubation, high glucose (27.5 or 55 mmol/l) alone induced an increase in NF-
B activity in VSMCs; this increase was mimicked by mannitol given to deliver the same osmolar stress to the cells. High glucose or mannitol also enhanced TNF
-stimulated NF-
B activity. Incubation with high glucose for 48 h followed by stimulation with TNF
led to a marked potentiation of NF-
B activation compared with normoglycemic (5.5 mmol/l) VSMCs exposed to TNF
, while mannitol attenuated this effect. A 48-h incubation with high glucose substantially reduced glutathione (GSH) levels compared with normoglycemic VSMCs, whereas mannitol significantly increased GSH levels. An antioxidant N-acetyl-L-cysteine and a selective protein kinase C (PKC) inhibitor GF109203X significantly suppressed the TNF
-induced NF-
B activation, and abrogated potentiation of TNF
-induced NF-
B activity caused by high glucose (27.5 mmol/l). Conclusion: These results suggest that acutely high glucose causes alterations in osmolarity leading to activation of NF-
B, but that exposure to high glucose for more prolonged times causes changes in antioxidant defences and activation of PKC, which potentiates cytokine activation of NF-
B. Further definition of these pathways will help to delineate important signals mediating the aberrant behavior of VSMCs under hyperglycemic/diabetic conditions.
KEYWORDS Vascular smooth muscle cells; Nuclear factor
B; High glucose; Glutathione; Protein kinase C
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
U. Hasler Controlled aquaporin-2 expression in the hypertonic environment Am J Physiol Cell Physiol, April 1, 2009; 296(4): C641 - C653. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. J. Francis, J. A. Martinez, W. Q. Liu, K. Xu, A. Ayer, J. Fine, U. I. Tuor, G. Glazner, L. R. Hanson, W. H. Frey II, et al. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy Brain, December 1, 2008; 131(12): 3311 - 3334. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Palazzo, S. Gariboldi, L. Zanobbio, S. Selleri, G. F. Dusio, V. Mauro, A. Rossini, A. Balsari, and C. Rumio Sodium-Dependent Glucose Transporter-1 as a Novel Immunological Player in the Intestinal Mucosa J. Immunol., September 1, 2008; 181(5): 3126 - 3136. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Dickinson, D. P Hancock, P. Petocz, A. Ceriello, and J. Brand-Miller High-glycemic index carbohydrate increases nuclear factor-{kappa}B activation in mononuclear cells of young, lean healthy subjects Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1188 - 1193. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. V. Ramana, R. Tammali, A. B. M. Reddy, A. Bhatnagar, and S. K. Srivastava Aldose Reductase-Regulated Tumor Necrosis Factor-{alpha} Production Is Essential for High Glucose-Induced Vascular Smooth Muscle Cell Growth Endocrinology, September 1, 2007; 148(9): 4371 - 4384. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nitenberg Macrovascular disease in type 2 diabetes: We do need animal models for in vivo studies Cardiovasc Res, February 1, 2007; 73(3): 450 - 452. [Full Text] [PDF] |
||||
![]() |
J. M. Starkey, S. J. Haidacher, W. S. LeJeune, X. Zhang, B. C. Tieu, S. Choudhary, A. R. Brasier, L. A. Denner, and R. G. Tilton Diabetes-Induced Activation of Canonical and Noncanonical Nuclear Factor-{kappa}B Pathways in Renal Cortex. Diabetes, May 1, 2006; 55(5): 1252 - 1259. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A Powell, K. M Warpeha, W. Xu, B. Walker, and E. R Trimble High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells J. Mol. Endocrinol., December 1, 2004; 33(3): 797 - 803. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. V. Ramana, B. Friedrich, S. Srivastava, A. Bhatnagar, and S. K. Srivastava Activation of Nulcear Factor-{kappa}B by Hyperglycemia in Vascular Smooth Muscle Cells Is Regulated by Aldose Reductase Diabetes, November 1, 2004; 53(11): 2910 - 2920. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF] |
||||
![]() |
M. A. Creager, T. F. Luscher, F. Cosentino, and J. A. Beckman Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I Circulation, September 23, 2003; 108(12): 1527 - 1532. [Full Text] [PDF] |
||||
![]() |
S. C. Pingle, J. F. Sanchez, D. M. Hallam, A. L. Williamson, S. B. Maggirwar, and V. Ramkumar Hypertonicity Inhibits Lipopolysaccharide-Induced Nitric Oxide Synthase Expression in Smooth Muscle Cells by Inhibiting Nuclear Factor {kappa}B Mol. Pharmacol., June 1, 2003; 63(6): 1238 - 1247. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Schiekofer, M. Andrassy, J. Chen, G. Rudofsky, J. Schneider, T. Wendt, N. Stefan, P. Humpert, A. Fritsche, M. Stumvoll, et al. Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor {kappa}B in PBMCs Diabetes, March 1, 2003; 52(3): 621 - 633. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Gunnett, D. D. Heistad, and F. M. Faraci Interleukin-10 Protects Nitric Oxide-Dependent Relaxation During Diabetes: Role of Superoxide Diabetes, June 1, 2002; 51(6): 1931 - 1937. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. R. James, D. Tang, A. Ingram, H. Ly, K. Thai, L. Cai, and J. W. Scholey Flux Through the Hexosamine Pathway Is a Determinant of Nuclear Factor {kappa}B- Dependent Promoter Activation Diabetes, April 1, 2002; 51(4): 1146 - 1156. [Abstract] [Full Text] [PDF] |
||||










