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No-Hee Park

Publications and source records attributed to No-Hee Park.

7 recordsLinked to original sources
PubMed2003

Senescence-associated genes in normal human oral keratinocytes.

The current study was undertaken to identify senescence-associated (SA) genes in cultured normal human oral keratinocytes (NHOK). Primary NHOK were serially subcultured in vitro as dispersed cells in low (0.15 mM) Ca(2+) medium until senescence. The SA genes of NHOK were identified by comparing the expression levels of 3195 human genes between exponentially replicating and senescing cultures. Approximately 5% of the screened genes were upregulated in senescing NHOK by a factor greater than 3 compared with rapidly dividing NHOK culture. Among them, we identified discrete gene groups, i.e., cyclin-dependent kinase inhibitors, G-protein-coupled receptors, apolipoproteins, matrix metalloproteinases, and mitochondrial proteins. To validate the microarray results, we confirmed the enhanced expression of a few selected SA genes, i.e., gpr1, apo-D, apo-E, apo-L, mmp-1, mmp-3, cyb561, cyp1b1, and cyp4b1, by reverse transcription-PCR. These SA genes were upregulated in three independent cultures of NHOK at high population doubling (PD) levels compared with those of low PDs. The enhanced expression of these SA genes was also found in senescing NHOK maintained in 3T3 feeder cell system, as well as in the chemically defined medium containing low Ca(2+). These results indicate that the onset of senescence in NHOK is associated with altered expression of the SA genes, which represent discrete gene groups, independently of the donor variation or culture conditions.

3T3 Cells↗
PubMed2003

Cytokine dependent inverse regulation of CD54 (ICAM1) and major histocompatibility complex class I antigens by nuclear factor kappaB in HEp2 tumor cell line: effect on the function of natural killer cells.

The aim of this study is to investigate the mechanisms by which elevated nuclear factor kappaB (NFkappaB) activity in HEp2 cells can modulate the function and survival of immune effector cells. Inhibition of NFkappaB functional activity by stable expression of IkappaB super-repressor rendered HEp2 cells (HEp2-IkappaB((S32AS36A))) susceptible to natural killer (NK) cell mediated cytotoxicity. Increase in surface ICAM1 expression was greater on HEp2-IkappaB((S32AS36A)) cells than on the surface of vector alone transfected HEp2 cells when these cells were treated with IFN-gamma. In contrast, tumor necrosis factor alpha (TNF-alpha) treatment augmented ICAM-1 expression on the surface of vector-alone transfected HEp2 cells and not on the HEp2-IkappaB((S32AS36A)) cells. Moreover, synergistic augmentation of ICAM-1 by a combination of TNF-alpha and interferon-gamma (IFN-gamma) treatment was completely abrogated on the surface of HEp2-IkappaB((S32AS36A)) cells. The addition of blocking antibody to ICAM-1 surface antigen partially inhibited the increased cytotxicity mediated by interleukin-2 treated NK cells against HEp2-IkappaB((S32AS36A)) cells. In contrast to ICAM-1, the expression of major histocompatibility complex (MHC) class I antigens were downregulated when the function of nuclear NFkappaB was inhibited in HEp2 cells. The addition of IFN-gamma to HEp2-kappaB((S32AS36A)) cells increased the expression of MHC class I antigen and rendered these cells less susceptible to NK cell mediated cytotoxicity. Secretion of IFN-gamma and granulocyte macrophage-colony-stimulating factor (GM-CSF) by NK cells was also significantly increased in the presence of HEp2-IkappaB((S32AS36A)) cells, and the treatment of these tumor cells with IFN-gamma prior to their addition to the cultures of NK cells decreased the released IFN-gamma and GM-CSF by NK cells. However, the levels of NK cell mediated cytotoxicity and IFN-gamma secretion remained significantly higher in the presence of both untreated and IFN-gamma treated HEp2-IkappaB((S32AS36A)) cells when compared with vector-alone transfected HEp2 cells. Thus, NFkappaB regulates inversely the expression of ICAM-1 and MHC class I antigens on HEp2 tumor cells and this may contribute to the resistance of these cells to NK cell mediated cytotoxicity.

Apoptosis↗
PubMed2003

Absence of hamTERT gene expression is associated with promoter hypermethylation in immortal hamster buccal pouch epithelial cells.

This study describes the first example of spontaneously immortalized, telomerase-negative hamster cells which replicated in the absence of telomere shortening. Primary hamster buccal pouch epithelial (HBPE) cells were subcultured for approximately 10 population doublings (PDs) before they ceased to divide. Among the non-replicating HBPE cells, a colony of proliferating cells had appeared. These cells named HBPE-SI (spontaneously immortalized) replicated with a mean doubling time of 27 h for 120 PDs in culture and are still replicating. Surprisingly, telomerase activity and hamTERT (hamster telomerase gene) expression were not detectable in HBPE-SI, although an exogenous hamTERT promoter showed promoter activity in these cells. HBPE-SI cells replicated in the apparent absence of apparent telomere shortening during their entire in vitro culture, indicating telomerase-independent mode of telomere maintenance. Analysis of the hamTERT promoter in HBPE-SI cells revealed hypermethylation. Exposure of the cells to 5-aza-2'-deoxycytidine (5-aza CdR) restored expression of endogenous hamTERT mRNA. These results indicated that HBPE-SI cells maintained their telomere length in the absence of telomerase activity, and that hamTERT gene expression in these cells was silenced by hypermethylation of the promoter.

Animals↗
PubMed2002

gp120-Independent infection of CD4(-) epithelial cells and CD4(+) T-cells by HIV-1.

Infection of CD4- cells by HIV-1 is well documented, but the mechanism responsible remains a matter of discussion. Previously we modified an HIV-1 virus strain, NL4-3, by deleting the Env proteins (gp41 and gp120) and inserting the enhanced green fluorescent protein (EGFP), and found that the Env(-) virus infects several types of CD4- cells. Here, we have prepared Env(-) virus from both the CD4- cell line, 293T, and the CD4+ cell lines, CEM and SUPT1, and found that HIV-1 Env(-) virus from either cell type is infectious for both CD4+ and several CD4- cell lines. Replication of HIV-1 Env(-) virus-infected cells was demonstrated by p24 gag protein assays and real-time reverse transcriptase polymerase chain reaction (RT-PCR) of the culture medium from infected cells. Virus collected from the HIV-1-Env(-) infected cultures proved infectious to several CD4- cell lines. Our results suggest that HIV-1 infects both CD4- and CD4+ cells using a gp120-independent mechanism. This infection mechanism may provide new explanations for HIV-1 latency and persistent infection in patients.

CD4 Antigens↗
PubMed2002

The telomeric length and heterogeneity decrease with age in normal human oral keratinocytes.

We have examined the telomere length in NHOK explanted from 28 donors between the ages of 21 and 84 years. Genomic DNA was isolated from exponentially replicating NHOK and digested with HinFI to yield terminal restriction fragments (TRF). The TRF length ranged from 4.1 to 7.0 kbp with a mean of 5.3 +/- 0.8 kbp, which was significantly shorter than that (8.9 +/- 1.0 kbp) of normal human oral fibroblasts (NHOF). The TRF length was inversely correlated to the increase of donor age in NHOK (m=-23 bp per year; r=-0.60; P<0.001). Also, the heterogeneity of TRF length in cultured NHOK decreased with increased donor age (r=-0.38, P<0.05). These data indicated that clonogenic NHOK cells had replicated in situ and showed a progressive shortening of TRF length. The short telomere length and decreased telomeric length heterogeneity in immortalized cells suggested that there is a critical minimum for cell survival.

Adult↗
PubMed2002

5.3 Global challenges in research and strategic planning.

Health sciences research is experiencing dramatic progress. How can dental schools throughout the world best make these research advances relevant for dental students, as well as providing them with the means to assess and utilize the research advances that will occur in the future? This complex question presents a critical challenge to the dental educational community. Research is clearly integral to the mission of dental education. By providing dental students with active learning strategies, dental educators can inculcate the ability for independent scientific thinking and thereby develop reflective as well as technically competent practitioners. However, there is a shortage of well-trained individuals to fill faculty and research positions in certain parts of the world. Global networks for mutual information exchange are imperative to overcome resource limitations in individual institutions, as is dedicated funding for research in the dental educational setting.

Computer Communication Networks↗