Biomedical subjects

Jae Youl Cho

Publications and source records attributed to Jae Youl Cho.

23 records · Page 2Linked to original sources

PubMed2003

Staurosporine induces rapid homotypic intercellular adhesion of U937 cells via multiple kinase activation.

1. Staurosporine is a broad-specificity kinase inhibitor, which has acted as lead compound for the development of some novel cytotoxic compounds for treatment of cancer. This study investigates the unexpected observation that staurosporine can also induce homotypic cellular aggregation. 2. In this study, staurosporine is shown to activate rapid homotypic aggregation of U937 cells, at concentrations below those required to induce cell death. This activity is a particular feature of staurosporine, and is not shared by a number of other kinase inhibitors. The proaggregating activity of staurosporine is inhibited by deoxyglucose, cytochalasin B and colchicine. Staurosporine-induced aggregation can be distinguished from that induced by the phorbol 12-myristate 13-acetate by faster kinetics and insensitivity to cycloheximide. Staurosporine induces translocation of conventional and novel, but not atypical isoforms of protein kinase C (PKC). Aggregation induced by staurosporine is inhibited by a number of inhibitors of PKC isoforms, and by inhibitors of protein tyrosine kinases. Staurosporine also induces rapid phosphorylation of ERK and p38, and inhibitors of both these enzymes block aggregation. 3. Staurosporine induces dysregulated activation of multiple kinase signaling pathways in U937 cells, and the combined activity of several of these pathways is essential for the induction of aggregation.

Acetophenones↗

PubMed2003

CD98-dependent homotypic aggregation is associated with translocation of protein kinase Cdelta and activation of mitogen-activated protein kinases.

CD98 is a protein found on the surface of many activated cell types, and is implicated in the regulation of cellular differentiation, adhesion, growth, and apoptosis. Despite many studies addressing CD98 function, there is little information on the intracellular signalling pathways that mediate its activity. In this study, we examine protein kinase pathways that are activated following ligation by the CD98 antibody AHN-18, an antibody that induces U937 homotypic aggregation and inhibits antigen presenting activity and T-cell activation. Ligation by CD98 antibody AHN-18 induces tyrosine kinase activity, but inhibition of this activity does not affect U937 aggregation. Ligation also induces membrane translocation of the serine/threonine kinase novel PKCdelta, but not other members of the PKC family. Translocation is blocked by rottlerin, and this inhibitor also blocks aggregation. PKCdelta activation in turn mediates activation of ERK1/2 and p38, as well as tyrosine phosphorylation of multiple proteins, and MAPK activation is essential for cellular aggregation. One of the targets of CD98-induced tyrosine phosphorylation is itself PKCdelta, suggesting that this phosphorylation may act as a negative feedback to limit the overall activation of the CD98 pathway.

Adrenergic beta-Antagonists↗

PubMed2003

Identification of cooperative monomeric Brachyury sites conferring T-bet responsiveness to the proximal IFN-gamma promoter.

The T-box transcription factor T-bet has been reported to augment the activity of IFN-gamma reporter constructs and to be required for CD4(+), but not CD8(+), T cell production for IFN-gamma. Despite these observations, the precise sequence targets of T-bet within the IFN-gamma locus have not been identified and the nature of T-bet's role in selectively augmenting IFN-gamma production in CD4(+) T cells has not been elucidated. As an initial step in this process, we examined the basis of T-bet-dependent augmentation of IFN-gamma reporter constructs to identify specific targets of this factor within the IFN-gamma locus. Deletion of previously proposed TDB and TRU elements left T-bet-induced IFN-gamma reporter activity unchanged, suggesting the existence of additional T-bet-responsive elements. We identified several additional monomeric Brachyury consensus elements within the proximal IFN-gamma promoter that operate cooperatively to increase both constitutive and stimulated promoter activity. The most proximal of these Brachyury elements is most significant quantitatively in mediating T-bet-dependent promoter augmentation. Mutation of this with any of the other Brachyury elements leads to a near eradication of T-bet-dependent promoter activation. The identification of these individual monomeric Brachyury-binding sites within the IFN-gamma locus should facilitate the in vivo analysis of the function of T-bet in the lineage- and background-dependent requirement for T-bet in IFN-gamma gene regulation.

Base Sequence↗

PubMed2002

Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation.

We have examined the immunosuppressive effects of representative ginsenosides (Rb1, Rb2, Re and Rg1) from Panax ginseng C. A. Meyer on CD4+ and CD8+ lymphocyte proliferation. Ginsenosides differentially modulated lymphocyte proliferation induced by concanavalin A (Con A), lipopolysaccharide (LPS), phytohemaglutinin (PHA) and interleukin-2 (IL-2). Thus, Rb1 and Re significantly enhanced Con A-induced lymphocyte proliferation, whereas Rg1 did not affect the proliferation. Interestingly, however, Rb2 strongly blocked Con A, LPS and PHA-induced lymphocyte proliferation with the IC50 values of 21.8, 29.0 and 24.0 microM, respectively. Moreover, Rb2 inhibited Con A-stimulated IL-2 production with an IC 50 of 13.3 microM. In the IL-2-stimulated CD8+ T cell (CTLL-2) proliferation assay, Re and Rg1 showed strong suppressive effects with IC50 values of 57.5 and 64.7 microM, respectively. In contrast, neither Rb1 nor Rb2 did inhibit CTLL-2 cell proliferation at tested concentrations. These results suggest that ginsenosides from P. ginseng may modulate lymphocyte proliferation in a different manner.

Animals↗

PubMed2002

Synthesis and SAR studies for the inhibition of TNF-alpha production. Part 2. 2-[3-(Cyclopentyloxy)-4-methoxyphenyl]-substituted-1-isoindolinone derivatives.

This study describes the synthesis and in vitro evaluation of 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of TNF-alpha production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-amino-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in inhibitory activity of TNF-alpha production in LPS-stimulated RAW264.7 cells.

Animals↗