Biomedical subjects

Young-Guen Kwon

Publications and source records attributed to Young-Guen Kwon.

42 records · Page 3Linked to original sources

PubMed2002

Interleukin-4 inhibits the vascular endothelial growth factor- and basic fibroblast growth factor-induced angiogenesis in vitro.

The role of interleukin-4 (IL-4) in the inflammatory process has emerged recently. In this study, we investigated the effect of IL-4 on the angiogenic process in an in vitro experimental system. IL-4 significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) that was induced by the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF- or bFGF-induced HUVEC chemotaxis was abrogated by the IL-4 treatment. In addition, the formation of tube-like structures by HUVEC in the presence of VEGF or bFGF was also severely down-regulated by IL-4. The inhibitory effects on the critical steps of angiogenesis were not observed with IL-6 that is abundantly found in the inflamed tissue. Our results suggest that IL-4 may play a regulatory role in normal physiology and provide the potential possibility for IL-4 as a therapeutic agent in the intervention of angiogenesis-related diseases.

Chemotaxis↗

PubMed2002

Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.

Endostatin, a fragment of collagen XVIII, is a potent anti-angiogenic protein, but the molecular mechanism of its action is not yet clear. We examined the effects of endostatin on the biological and biochemical activities of vascular endothelial growth factor (VEGF). Endostatin blocked VEGF-induced tyrosine phosphorylation of KDR/Flk-1 and activation of ERK, p38 MAPK, and p125(FAK) in human umbilical vein endothelial cells. Endostatin also inhibited the binding of VEGF(165) to both endothelial cells and purified extracellular domain of KDR/Flk-1. Moreover, the binding of VEGF(121) to KDR/Flk-1 and VEGF(121)-stimulated ERK activation were blocked by endostatin. The direct interaction between endostatin and KDR/Flk-1 was confirmed by affinity chromatography. However, endostatin did not bind to VEGF. Our findings suggest that a direct interaction of endostatin with KDR/Flk-1 may be involved in the inhibitory function of endostatin toward VEGF actions and responsible for its potent anti-angiogenic and anti-tumor activities in vivo.

Antineoplastic Agents↗

PubMed2002

Regulation of apoptosis by nitrosative stress.

Nitrosative stress can prevent or induce apoptosis. It occurs via S-nitrosylation by the interaction of nitric oxide (NO) with the biological thiols of proteins. Cellular redox potential and non-heme iron content determine S-nitrosylation. Apoptotic cell death is inhibited by S-nitrosylation of the redox-sensitive thiol in the catalytic site of caspase family proteases, which play an essential role in the apoptotic signal cascade. Nitrosative stress can also promote apoptosis by the activation of mitochondrial apoptotic pathways, such as the release of cytochrome c, an apoptosis-inducing factor, and endonuclease G from mitochondria, as well as the suppression of NF-kB activity. In this article we reviewed the mechanisms whereby S-nitrosylation and nitrosative stress regulate the apoptotic signal cascade.

Animals↗

PubMed2002

Regulation of caspases by nitric oxide.

Nitric oxide can prevent or induce apoptosis depending on its concentration, cell type, and the oxidative milieu. Nitric oxide inhibits apoptosis and inflammation by S-nitrosylation of the active site cysteine of caspases, the central effector molecules of cell death as well as maturation of IL-1beta and IL-18. The ability of nitric oxide to S-nitrosylate caspases depends on multiple factors including the presence of free iron and intracellular redox potential. There are no known direct effects of nitric oxide on promoting caspase activation or activity. However, nitric oxide has been shown to promote apoptotic pathways in numerous cell types through the indirect activation of caspases. In this article we review the relationship of nitric oxide and caspase activity, modulation of this effect by iron, and clinical implications for the use of nitric oxide in regulating inflammation and apoptosis.

Animals↗

PubMed2001

TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells.

Angiogenesis is an essential step for many physiological and pathological processes. Tumor necrosis factor (TNF) superfamily cytokines are increasingly recognized as key modulators of angiogenesis. In this study, we tested whether TNF-related activation-induced cytokine (TRANCE), a new member of the TNF superfamily, possesses angiogenic activity in vitro and in vivo. TRANCE stimulated DNA synthesis, chemotactic motility, and capillary-like tube formation in primary cultured human umbilical vein endothelial cells (HUVECs). Both Matrigel plug assay in mice and chick chorioallantoic membrane assay revealed that TRANCE potently induced neovascularization in vivo. TRANCE had no effect on vascular endothelial growth factor (VEGF) expression in HUVECs and TRANCE-induced angiogenic activity was not suppressed by VEGF-neutralizing antibody, implying that TRANCE-induced angiogenesis may be the result of its direct action on endothelial cells. TRANCE evoked a time- and dose-dependent activation of the mitogen-activated protein kinases ERK1/2 and focal adhesion kinase p125(FAK) in HUVECs, which are closely linked to angiogenesis. These signaling events were blocked by the Src inhibitor PP1 or the phospholipase C (PLC) inhibitor. Furthermore, these inhibitors and the Ca(2+) chelator BAPTA-AM suppressed TRANCE-induced HUVEC migration. These results indicate that the angiogenic activity of TRANCE is mediated through the Src-PLC-Ca(2+) signaling cascade upon receptor engagement in endothelial cells, suggesting the role of TRANCE in neovessel formation under physiological and pathological conditions.

Calcium↗

PubMedDate not supplied

Regulation of programmed cell death in neuronal cells by nitric oxide.

Nitric oxide (NO), produced from L-arginine and molecular oxygen in a reaction catalyzed by one of three NO synthase isoenzymes, can prevent or induce neuronal apoptosis depending on its concentration and cellular redox state. This molecule affords neuroprotection by post-translational S-nitrosylation of NMDA receptor, caspases and p21ras, and increases the expression of cytoprotective genes such as HSP70, heme oxygenase and Bcl-2. Moreover, the NO/cGMP pathway activates the anti-apoptotic serine/threonine kinase Akt by protein kinase G-dependent activation of phosphatidylinositol 3-kinase. A high concentration of NO and peroxynitrite, a reaction product of NO with superoxide anion, can promote apoptotic pathways in neuronal cells through the indirect activation of caspases. We review the molecular mechanism by which NO exerts both pro- and anti-apoptotic actions in neuronal cells and the clinical implications for regulating neuronal apoptosis.

Animals↗