High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase

McGinn, S., Saad, S., Poronnik, P. and Pollock, C. A. (2003) High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase. American Journal of Physiology-endocrinology And Metabolism, 285 4: E708-E717. doi:10.1152/ajpendo.00572.2002


Author McGinn, S.
Saad, S.
Poronnik, P.
Pollock, C. A.
Title High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase
Journal name American Journal of Physiology-endocrinology And Metabolism   Check publisher's open access policy
ISSN 0193-1849
Publication date 2003-10-01
Year available 2003
Sub-type Article (original research)
DOI 10.1152/ajpendo.00572.2002
Open Access Status Not yet assessed
Volume 285
Issue 4
Start page E708
End page E717
Total pages 10
Place of publication Washington
Publisher American Physiological Society
Language eng
Subject C1
321012 Nephrology and Urology
730106 Cardiovascular system and diseases
730115 Urogenital system and disorders
Abstract The mitogen-activated protein ( MAP) kinases contribute to altered cell growth and function in a variety of disease states. However, their role in the endothelial complications of diabetes mellitus remains unclear. Human endothelial cells were exposed for 72 h to 5 mM ( control) or 25 mM ( high) glucose or 5 mM glucose plus 20 mM mannitol ( osmotic control). The roles of p38 and p42/44 MAP kinases in the high glucose-induced growth effects were determined by assessment of phosphorylated MAP kinases and their downstream activators by Western blot and by pharmacological inhibition of these MAP kinases. Results were expressed as a percentage ( means +/- SE) of control. High glucose increased the activity of total and phosphorylated p38 MAP kinase ( P < 0.001) and p42/44 MAP kinase ( P < 0.001). Coexposure of p38 MAP kinase blocker with high glucose reversed the antiproliferative but not the hypertrophic effects associated with high-glucose conditions. Transforming growth factor (TGF)-beta1 increased the levels of phosphorylated p38 MAP kinase, and p38 MAP kinase blockade reversed the antiproliferative effects of this cytokine. The high glucose-induced increase in phosphorylated p38 MAP kinase was reversed in the presence of TGF-beta1 neutralizing antibody. Although hyperosmolarity also induced antiproliferation (P < 0.0001) and cell hypertrophy (P < 0.05), there was no change in p38 activity, and therefore inhibition of p38 MAP kinase had no influence on these growth responses. Blockade of p42/44 MAP kinase had no effect on the changes in endothelial cell growth induced by either high glucose or hyperosmolarity. High glucose increased p42/44 and p38 MAP kinase activity in human endothelial cells, but only p38 MAP kinase mediated the antiproliferative growth response through the effects of autocrine TGF-beta1. High glucose-induced endothelial cell hypertrophy was independent of activation of the MAP kinases studied. In addition, these effects were independent of any increase in osmolarity associated with high-glucose exposure.
Keyword Endocrinology & Metabolism
Physiology
High Glucose
Endothelial Cell
Growth
P38 Mitogen-activated Protein Kinase
P42/44 Mitogen-activated Protein Kinase
Transforming Growth Factor-beta 1
Activated Protein-kinases
Growth-factor
Tgf-beta
Cycle
Culture
Phosphorylation
Identification
Tgf-beta-1
Apoptosis
Induction
Q-Index Code C1
Additional Notes DOI: 10.1152/ajpendo.00572.2002

 
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Created: Wed, 15 Aug 2007, 12:25:49 EST