Biomedical subjects

Sang Keun Kim

Publications and source records attributed to Sang Keun Kim.

4 recordsLinked to original sources

PubMed2006

Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes.

Regulators of G protein signaling (RGSs) are inducibly expressed in response to various stimuli and the up-regulation of RGSs leads to significant decreases in GPCR responsiveness. Isoproterenol, an adrenergic receptor agonist, stimulated RGS2 mRNA in C6 rat astrocytoma cells. The up-regulation of RGS2 mRNA was abrogated by genistein, a protein tyrosine kinase inhibitor (PTK), and by broad-spectrum protein kinase C (PKC) inhibitors (staurosporine and GF109203X). alpha-Adrenergic antagonist (prazocin), beta-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by Galphai, Galphas, and Galphaq. It is interesting to note that SB203580, a potent p38 mitogen-activated protein kinase (MAPK) inhibitor, completely inhibited the isoproterenol-mediated RGS2 expression. In addition, isoproterenol also markedly stimulated RGS2 mRNA in rat primary astrocytes, which were sensitive to SB203580 and staurosporine. Therefore, our data suggest that adrenergic receptor-mediated signaling (induced by isoproterenol) may be involved in the regulation of RGS2 expression in astrocytes via activating PTK, PKC, and p38 MAPK.

Animals↗

PubMed2006

BRCA1 modulates xenobiotic stress-inducible gene expression by interacting with ARNT in human breast cancer cells.

Previously, we have reported that BRCA1 regulates the expression of various classes of genes, including genes involved in xenobiotic stress responses (Bae, I., Fan, S., Meng, Q., Rih, J. K., Kim, H. J., Kang, H. J., Xu, J., Goldberg, I. D., Jaiswal, A. K., and Rosen, E. M. (2004) Cancer Res. 64, 7893-7909). In the present study, we have investigated the effects of BRCA1 on xenobiotic stress-inducible gene expression. In response to aryl hydrocarbon receptor (AhR) ligands, cytoplasmic AhR becomes activated and then translocates to the nucleus where it forms a complex with the aryl hydrocarbon receptor nuclear translocator (ARNT). Subsequently, the AhR.ARNT complex binds to the enhancer or promoter of genes containing a xenobiotic stress-responsive element and regulates the expression of multiple target genes including cytochrome P450 subfamily polypeptide 1 (CYP1A1). In this study, we have found that endogenous and overexpressed exogenous wild-type BRCA1 affect xenobiotic stress-induced CYP1A1 gene expression. Using a standard chromatin immunoprecipitation assay, we have demonstrated that BRCA1 is recruited to the promoter regions of CYP1A1 and CYP1B1 along with ARNT and/or AhR following xenobiotic exposure. Our findings suggest that BRCA1 may be physiologically important for mounting a normal response to xenobiotic insults and that it may function as a coactivator for ARNT activity. Using immunoprecipitation, Western blotting, and glutathione S-transferase capture assays, a xenobiotic-independent interaction between BRCA1 and ARNT has been identified, although it is not yet known whether this is a direct or indirect interaction. We have also found that the inducibility of CYP1A1 and CYP1B1 transcripts following xenobiotic stress was significantly attenuated in BRCA1 knockdown cells. This reduced inducibility is associated with an altered stability of ARNT and was almost completely reversed in cells transfected with an ARNT expression vector. Finally, we have found that xenobiotic (TCDD) treatments of breast cancer cells containing reduced levels of BRCA1 cause the transcription factor ARNT to become unstable.

Aryl Hydrocarbon Receptor Nuclear Translocator↗

PubMed2006

The expression patterns of RGS transcripts in platelets.

Regulators of G protein signalling (RGS) are involved in the negative regulation of cell activation processes and are involved in the pathophysiology of cardiovascular diseases. To get some further evidence for a role of RGS proteins in platelets, we determined the expression profile of RGS-specific mRNA in rat platelets using reverse transcription-polymerase chain reaction (RT-PCR) with a poly dT18 primer and transcript-specific primers. We found that RGS2, RGS3, RGS5, RGS6, RGS10, RGS14, RGS16 and RGS18, Leukemia-associated Rho-GEF factor (LARG), and Galpha interacting protein (GAIP) were differentially expressed in platelets. The highest expression rate was found for RGS18 (about 1.3 fold when compared to GAPDH), followed by LARG, RGS6, RGS10 and RGS16 (0.7 to 0.95), whereas expression rates for RGS2, RGS3, RGS5, RGS14, and GAIP were in a range of 0.1 to 0.3. Our results suggest that G-protein-coupled receptor-mediated signalling in platelet may be regulated mainly by RGS 18, 16, 10, 6, and LARG.

Animals↗

PubMed2006

Surfactin C inhibits platelet aggregation.

This study was designed to investigate the effect of surfactin C, which is derived from Bacillus subtilis, on platelet aggregation and homotypic leucocyte aggregation. Surfactin C strongly and dose-dependently inhibited platelet aggregation, which was stimulated both by thrombin (0.1 U mL(-1)), a potent agonist that activates the G protein-coupled protease receptor, and by collagen (5 microg mL(-1)), a potent ligand that activates alpha(IIb)beta(3) with IC50 values (concentration inhibiting platelet aggregation by 50%) of 10.9 and 17.0 microM, respectively. Moreover, surfactin C significantly suppressed the intracellular Ca(2+) mobilization in thrombin-activated platelets. Surfactin C, however, did not affect various integrin-mediated U937 cell aggregation, implying that the anti-platelet activity of surfactin C was not due to its detergent effect but by its action on the downstream signalling pathway. Therefore, the results suggest that surfactin C may have a beneficial therapeutic effect on aberrant platelet aggregation-mediated cardiovascular diseases.

Animals↗