Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 44, Issue 12, Pages 2043-2050Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.03.014
Keywords
honokiol; human umbilical vein endothelial cells; hyperglycemia; NADPH oxidase; reactive oxygen species; NF-kappa B; cyclooxygenase-2; apoptosis
Ask authors/readers for more resources
Angiopathy is a major complication of diabetes. Abnormally high blood glucose is a crucial risk factor for endothelial cell damage. Nuclear factor-kappa B (NF-kappa B) has been demonstrated as a mediated signaling in hyperglycemia or oxidative stress-triggered apoptosis of endothelial cells. Here we explored the efficacy of honokiol, a small molecular weight natural product, on NADPH oxidase-related oxidative stress-mediated NF-kappa B-regulated signaling and apoptosis in human umbilical vein endothelial cells (HUVECs) under hyperglycemic conditions. The methods of morphological Hoechst staining and annexin V/propidium iodide staining were used to detect apoptosis. Submicromolar concentrations of honokiol suppressed the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22(phox) protein expression, and reactive oxygen species production in high glucose (HG)-stimulated HUVECs. The degradation of I kappa B alpha and increase of NF-K beta activity were inhibited by honokiol in HG-treated HUVECs. Moreover, honokiol (0.125-1 mu M) also suppressed HG-induced cyclooxygenase (COX)-2 upregulation and prostaglandin E-2 production in HUVECs. Honokiol could reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by HG. These results imply that inhibition of NADPH oxidase-related oxidative stress by honokiol suppresses the HG-induced NF-kappa B-regulated COX-2 upregulation, apoptosis, and cell death in HUVECs, which has the potential to be developed as a therapeutic agent to prevent hyperglycemia-induced endothelial damage. (C) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available