21 Medical Science Education Center
21 Medical Science Education Center
Seo K.W.,Pusan National University |
Seo K.W.,21 Medical Science Education Center |
Lee S.J.,Pusan National University |
Lee S.J.,21 Medical Science Education Center |
And 12 more authors.
Atherosclerosis | Year: 2010
5-Lipoxygenase (5-LO) has been suggested as a modulator of atherosclerotic plaque instability, however, its role in MMP production in vascular smooth muscle cells (VSMC) is still unclear. Thus, this study investigated the role of 5-LO in HNE-enhanced MMP-2 production in VSMC, and the mechanisms by which this enzyme could be activated by HNE. VSMC stimulated with HNE (1 μM) produced MMP-2, which was markedly attenuated in 5-LO-deficient VSMC as well as in cells pretreated with a FLAP inhibitor, MK886, confirming a role for 5-LO metabolites in HNE-enhanced MMP-2 production. Related to these results, HNE increased nuclear translocation of 5-LO promoting 5-LO activity, which was attenuated not only by SB203580, a p38 MAPK inhibitor, but also by PD98059, an ERK inhibitor. In parallel, phosphorylation of p38 MAPK and ERK occurred as early as 15 min after exposure to HNE, suggesting a potential role for p38 MAPK and ERK pathways in HNE-induced activation of 5-LO. Among leukotriene (LT) receptor antagonists, U-75302, a BLT receptor antagonist, but not MK-571 and Rev-5901, cysLT receptor antagonists, showed an inhibitory effect on HNE-enhanced MMP-2 production. Moreover, MMP-2 production in VSMC was also significantly increased by LTB4, but not by LTC4 and LTD4. Collectively, these data suggest that 5-LO mediates HNE-enhanced MMP-2 production via LTB4-BLT receptor pathways, consequently leading to atherosclerotic plaque instability. © 2009 Elsevier Ireland Ltd. All rights reserved.
Park J.Y.,Pusan National University |
Park J.Y.,21 Medical Science Education Center |
Kim M.J.,Pusan National University |
Kim Y.K.,Pusan National University |
And 2 more authors.
Archives of Toxicology | Year: 2011
Apoptosis of stem cells may be related to certain degenerative conditions such as progressive tissue damage and an inability to repair. Ceramide induces cell death in various cell types. However, the underlying mechanisms of ceramide-induced cell death in stem cells are not explored. This study was designed to investigate the cell death process caused by cell-permeable ceramide and to determine the underlying mechanisms in mesenchymal stem cells derived from human adipose tissue (hASCs). Ceramide caused a loss of cell viability in a concentration- and time-dependent manner, which was largely attributable to apoptosis. Ceramide induced generation of reactive oxygen species (ROS) and disruption of the mitochondrial membrane potential. The ROS generation caused by ceramide was prevented by the antioxidant N-acetylcysteine (NAC). Although ceramide induced release of cytochrome c from mitochondria and activation of caspase-3, the ceramide-induced cell death was partially prevented by caspase inhibitors. Addition of ceramide caused apoptosis-inducing factor (AIF) nuclear translocation, which was prevented by antioxidant. Taken together, these data suggest that ceramide induces cell death through both caspase-dependent and caspase-independent mechanisms mediated by ROS generation in hASCs. © 2011 Springer-Verlag.
Cho H.H.,Pusan National University |
Cho H.H.,Medical Research Center for Ischemic Tissue Regeneration |
Shin K.K.,Pusan National University |
Shin K.K.,Medical Research Center for Ischemic Tissue Regeneration |
And 15 more authors.
Journal of Cellular Physiology | Year: 2010
Tumor necrosis factor-alpha (TNF-α) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF-α inhibits the mineralization of osteoblasts, the effect of TNF-α on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF-α on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF-κB activation on TNF-κ activity. TNF-κ treatment dose-dependently increased osteogenic differentiation over the first 3 days of treatment. TNF-κ activated ERK and increased NF-κB promoter activity. PDTC, an NF-κB inhibitor, blocked the osteogenic differentiation induced by TNF-α and TLR-ligands, but U102, an ERK inhibitor, did not. Overexpression of miR-146a induced the inhibition of IRAK1 expression and inhibited basal and TNF-α- and TLR ligand-induced osteogenic differentiation. TNF-α and TLR ligands increased the expression of transcriptional coactivator with PDZ-binding motif (TAZ), which was inhibited by the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter. TNF-α also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF-α enhances osteogenic differentiation of hADSC via the activation of NF-κB and a subsequent increase of TAZ expression. © 2010 Wiley-Liss, Inc.