Biomedical subjects

Han-A Kim

Publications and source records attributed to Han-A Kim.

4 recordsLinked to original sources

PubMed2007

Critical role for matrix metalloproteinase-9 in platelet-activating factor-induced experimental tumor metastasis.

In this study, the roles of matrix metalloproteinase (MMP)-2 and MMP-9 in platelet-activating factor (PAF)-induced experimental pulmonary metastasis of the murine melanoma cell, B16F10, were investigated. An injection of PAF resulted in increases in mRNA expression, protein levels and the activities of both MMP-2 and MMP-9 in the lungs. The overall expression of MMP-9 was stronger than that of MMP-2. The increased MMP-9 expression was inhibited by both NF-kappaB and AP-1 inhibitors, whereas the increased MMP-2 expression was inhibited by only AP-1 inhibitors. Immunohistochemical analysis revealed that MMP-9 was expressed in bronchial epithelial cells as well as in the walls of blood vessels, whereas MMP-2 expression was observed only in bronchial epithelial cells. PAF significantly enhanced the pulmonary metastasis of B16F10, which was inhibited by both NF-kappaB and c-jun inhibitors. MMP-9 inhibitor, but not that of MMP-2, completely inhibited PAF-induced B16F10 metastasis. These data indicate that MMP-9, the expression of which was regulated by NF-kappaB and AP-1, plays a critical role in PAF-induced enhancement of pulmonary melanoma metastasis.

Animals↗

PubMed2006

Platelet-activating factor induces up-regulation of antiapoptotic factors in a melanoma cell line through nuclear factor-kappaB activation.

In this study, we investigated the influence of platelet-activating factor (PAF) on the induction of apoptosis-regulating factors in B16F10 melanoma cells. PAF increased the expression of mRNA and the protein synthesis of antiapoptotic factors, such as Bcl-2 and Bcl-xL, but did not increase the expression of the proapoptotic factor, Bax. A selective nuclear factor-kappaB (NF-kappaB) inhibitor, parthenolide, inhibited the effects of PAF. Furthermore, PAF inhibited etoposide-induced increases in caspase-3, caspase-8, and caspase-9 activities, as well as cell death. p50/p65 heterodimer increased the mRNA expression of Bcl-2 and Bcl-xL and decreased etoposide-induced caspase activities and cell death. In an in vivo model in which Matrigel was injected s.c., PAF augmented the growth of B16F10 cells and attenuated etoposide-induced inhibition of B16F10 cells growth. These data indicate that PAF induces up-regulation of antiapoptotic factors in a NF-kappaB-dependent manner in a melanoma cell line, therefore suggesting that PAF may diminish the cytotoxic effect of chemotherapeutic agents.

Animals↗

PubMed2006

Platelet-activating factor-induced NF-kappaB activation enhances VEGF expression through a decrease in p53 activity.

We investigated the role of p53 in nuclear factor (NF)-kappaB dependent, platelet-activating factor (PAF)-induced vascular endothelial growth factor (VEGF) expression. Transfected NF-kappaB subunits in ECV304 cells increased the tumor necrosis factor-alpha promoter activity, which was completely inhibited by p53. Transfected p53 increased p53RE promoter activity, which was completely inhibited by NF-kappaB subunits, indicating that cross-regulation occurs between NF-kappaB and p53. PAF-induced increase in VEGF expression was correlated with decreased p53 activity. These data suggest that NF-kappaB-dependency of the PAF-induced increase in VEGF expression is due to decreased p53 activity, which is reciprocally regulated by increased NF-kappaB activity.

Cells, Cultured↗

PubMed2005

Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced angiogenesis.

Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of various angiogenic factors, via the activation of NF-kappaB. In this study, we investigated the role of the matrix metalloproteinase (MMP)-9, in PAF-induced angiogenesis. PAF increased mRNA expression, protein synthesis, and MMP-9 activity in ECV304 cells, in a NF-kappaB-dependent manner. PAF increased MMP-9 promoter activity in ECV304, which was inhibited by WEB2107, and NF-kappaB inhibitors. Transfected NF-kappaB subunits, p65 or/and p50, increased luciferase activity in the reporter plasmid MMP-9, resulting in an increase not only of MMP-9 luciferase activity, but also of mRNA expression in MMP-9. MMP-9 or NF-kappaB inhibitors significantly inhibited PAF-induced angiogenesis, in a dose-dependent manner, in an in vivo mouse Matrigel implantation model. In a parallel to the Matrigel implantation study, MMP-9 or NF-kappaB inhibitors inhibited PAF-induced sprouting of porcine pulmonary arterial endothelial cells. These data indicate that NF-kappaB-dependent MMP-9 plays a key role in PAF-induced angiogenesis.

Animals↗