Opposite effects of high glucose on MMP-2 and TIMP-2 in human endothelial cells
Journal
Journal of Cellular Biochemistry
Journal Volume
101
Journal Issue
2
Pages
442-450
Date Issued
2007
Author(s)
Abstract
Diabetes mellitus (DM) is a major risk factor for atherosclerosis and causes multiple cardiovascular complications. Although high glucose can induce matrix metalloproteinases (MMPs), its inhibitors and cell apoptosis, little is known about the roles of MMPs in regulating cell apoptosis in response to high glucose. To address this issue, we elucidated the relationship between MMPs, its inhibitors and cell apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with medium containing 5.5 mM or 33 mM of glucose in the presence or the absence of ascorbic acid and MMP inhibitors (GM6001 and endogenous tissue inhibitors of MMPs, TIMP-1, and TIMP-2). For detection of cell apoptosis, the cell death detection ELISA assay was used. The results revealed that high glucose-induced apoptosis could be suppressed by ascorbic acid, GM6001 and TIMP-2, but not by TIMP-1. The activities of MMP-2, MMP-9 and its inhibitors, TIMP-1, TIMP-2 after high glucose treatment, were also detected by ELISA method. We found that the activated form of MMP-2, but not MMP-9, was increased, while the level of TIMP-2, but not TIMP-1, was decreased. In Western blot and RT-PCR analysis, the expression of TIMP-2, but not TIMP-1, after high glucose treatment was downregulated, whereas the levels of MMP-2 and-9 proteins and mRNA were not changed. The present study indicated that oxidative stress induced by high glucose might be involved in the opposite effects on MMP-2 activation and TIMP-2 downregulation. This reactive oxygen species (ROS)-dependent MMP-2 activation in turn mediates high glucose-induced cell apoptosis in HUVECs. ? 2007 wiley-Liss, Inc.
SDGs
Other Subjects
ascorbic acid; gelatinase A; gelatinase B; glucose; ilomastat; reactive oxygen metabolite; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; apoptosis; article; controlled study; culture medium; down regulation; endothelium cell; enzyme activation; enzyme activity; enzyme linked immunosorbent assay; human; human cell; oxidative stress; priority journal; protein expression; reverse transcription polymerase chain reaction; umbilical vein; Western blotting; Cells, Cultured; Endothelial Cells; Enzyme Activation; Gene Expression Regulation; Glucose; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Oxidative Stress; Reactive Oxygen Species; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2
Type
journal article