Diabetes, Vol 36, Issue 11 1261-1267, Copyright © 1987 by American Diabetes Association

ARTICLES

High glucose prolongs cell-cycle traversal of cultured human endothelial cells

M Lorenzi, JA Nordberg and S Toledo
Department of Medicine, University of California, San Diego.

There is evidence suggesting that the diabetic state adversely affects replication of certain cell populations. We document that exposure to high ambient glucose (20 mM) induces delay in various phases of the cell cycle of human endothelial cells in primary culture. Cells in S phase were labeled with bromodeoxyuridine (an analogue of thymidine), and the cell-cycle position of the labeled cohort was analyzed by flow cytometry at successive time points. The movement of cells exposed to high glucose for 7-8 days was retarded both in S and G2 phases so that the increase in bromodeoxyuridine-positive cells over 24 h was 1.6-fold, versus 2.0-fold in control cultures. In experiments in which mitotic arrest with vinblastine was used to investigate the movement of cells out of G1 phase without interference from reentering cells, depletion of the G1 compartment was significantly inhibited in cultures grown in high glucose. The effects of chronic high glucose on cell cycle occurred while total protein synthesis was not diminished. Acute exposure to high glucose had no effect on cell-cycle traversal or cell generation time. Cell-cycle abnormalities observed in this study may relate to the DNA damage we have previously observed in endothelial cells exposed to high glucose and, if occurring in vivo, could be of pathogenetic importance for the vascular lesions and teratogenicity of diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions Cardiovasc Res, May 1, 2008; 78(2): 257 - 264. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

				A. J. Laing, J. P. Dillon, E.T. Condon, J. C. Coffey, J. T. Street, J. H. Wang, A. J. McGuinness, and H. P. Redmond A systemic provascular response in bone marrow to musculoskeletal trauma in mice J Bone Joint Surg Br, January 1, 2007; 89-B(1): 116 - 120. [Abstract] [Full Text] [PDF]

				J. Zhou, B. K. Deo, K. Hosoya, T. Terasaki, I. G. Obrosova, F. C. Brosius III, and A. K. Kumagai Increased JNK Phosphorylation and Oxidative Stress in Response to Increased Glucose Flux through Increased GLUT1 Expression in Rat Retinal Endothelial Cells Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3403 - 3410. [Abstract] [Full Text] [PDF]

				N. Krankel, V. Adams, A. Linke, S. Gielen, S. Erbs, K. Lenk, G. Schuler, and R. Hambrecht Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 698 - 703. [Abstract] [Full Text] [PDF]

				N. G. Abraham, T. Kushida, J. McClung, M. Weiss, S. Quan, R. Lafaro, Z. Darzynkiewicz, and M. Wolin Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells Circ. Res., September 19, 2003; 93(6): 507 - 514. [Abstract] [Full Text] [PDF]

				S. McGinn, P. Poronnik, M. King, E. D. M. Gallery, and C. A. Pollock High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity Am J Physiol Cell Physiol, June 1, 2003; 284(6): C1374 - C1386. [Abstract] [Full Text] [PDF]

				R. S. Marinos, W. Zhang, G. Wu, K. A. Kelly, and C. J. Meininger Tetrahydrobiopterin levels regulate endothelial cell proliferation Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H482 - H489. [Abstract] [Full Text] [PDF]

				J. Christopher, V. Velarde, D. Zhang, D. Mayfield, R. K. Mayfield, and A. A. Jaffa Regulation of B2-kinin receptors by glucose in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1537 - H1546. [Abstract] [Full Text] [PDF]

				M. Zanetti, R. M. Zwacka, J. F. Engelhardt, Z. S. Katusic, and T. O'Brien Superoxide Anions and Endothelial Cell Proliferation in Normoglycemia and Hyperglycemia Arterioscler. Thromb. Vasc. Biol., February 1, 2001; 21(2): 195 - 200. [Abstract] [Full Text] [PDF]

				W. Liu, A. Schoenkerman, and W. L. Lowe Jr. Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E782 - E790. [Abstract] [Full Text] [PDF]

				Q. di Wu, J. H. Wang, F. Fennessy, H. P. Redmond, and D. Bouchier-Hayes Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1229 - C1238. [Abstract] [Full Text] [PDF]

				A. Rivard, M. Silver, D. Chen, M. Kearney, M. Magner, B. Annex, K. Peters, and J. M. Isner Rescue of Diabetes-Related Impairment of Angiogenesis by Intramuscular Gene Therapy with Adeno-VEGF Am. J. Pathol., February 1, 1999; 154(2): 355 - 363. [Abstract] [Full Text] [PDF]