Biomedical subjects

Hun-Taeg Chung

Publications and source records attributed to Hun-Taeg Chung.

At least 55 records · Page 3Linked to original sources

PubMed2004

4-Acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol from Isaria japonica mediates apoptosis of rat bladder carcinoma NBT-II cells by decreasing anti-apoptotic Bcl-2 expression and increasing pro-apoptotic Bax expression.

We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.

Animals↗

PubMed2003

The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and may be selectively expressed on Th2 cells. In the present study, we analyzed the association of allele and genotype frequencies between asthma or atopy patients and the controls without asthma and atopy using large sample size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. Although the allele frequency of 5509_5511delCAA variation in asthma was not significantly different (P=0.085), the genotype of 5509_5511delCAA variation in asthma was significantly associated with the susceptibility to asthma (P=0.037). The genotype and allele frequencies of 5383_5397del variation in atopic dermatitis were significantly different from those in the non-asthmatic and non-atopic controls (P=0.005 and P=0.002, respectively). Our results strongly suggest that the 5383_5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility.

Asthma↗

PubMed2003

Catalposide protects Neuro 2A cells from hydrogen peroxide-induced cytotoxicity via the expression of heme oxygenase-1.

Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae) has been shown to possess anti-microbial, anti-tumoral, and anti-inflammatory properties. Heme oxygenase-1 (HO-1) is a stress response protein and is known to play a protective role against the oxidative injury. In this study, we examined whether catalposide could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 protein expression and HO activity. The treatment of the cells with catalposide resulted in dose- and time-dependent up-regulations of both HO-1 protein expression and HO activity. Catalposide protected the cells from hydrogen peroxide-induced cell death. The protective effect of catalposide on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Additional experiments revealed the involvement of CO in the cytoprotective effect of catalposide-induced HO-1. These results indicate that catalposide is a potent inducer of HO-1 and HO-1 induction is responsible for the catalposide-mediated cytoprotection against oxidative damage.

Animals↗

PubMed2003

Differential expressions of heme oxygenase-1 gene in CD25- and CD25+ subsets of human CD4+ T cells.

Growing evidence suggests that the immunomodulatory heme oxygenase-1 (HO-1) may have an important role in regulating T-cell responses. In this study, we investigated whether CD4(+)CD25(-) and CD4(+)CD25(+) T cells of human CD4(+) subpopulation could differentially express HO-1. Our results obtained from qualitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses revealed that the CD4(+)CD25(+) T cells constitutively express HO-1 and that T cell stimulation with plate-bound anti-CD3 in combination with soluble anti-CD28 not only induced HO-1 gene expression in the CD4(+)CD25(-) T cells but also up-regulated HO-1 gene expression in the CD4(+)CD25(+) T cells. Our further studies showed that CD28 signal alone was enough to induce HO-1 expression and CD3 signal, of which signal alone did not induce HO-1 expression, was required at least for full HO-1 expression in both CD25(-) and CD25(+) subsets of human CD4(+) T cells. In addition, transfection of human Jurkat T cells with HO-1 suppressed the cellular proliferation, and this effect was reversed by zinc protoporphyrin, a specific HO competitive inhibitor. Taken together, we have first reported that human CD4(+)CD25(+) regulatory T cells constitutively express HO-1 and that HO-1 inhibits Jurkat T cell proliferation.

CD28 Antigens↗

PubMed2003

Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-kappaB activation.

Cordyceps pruinosa has been used in traditional folk medicine to treat numerous diseases. The molecular mechanism of C. pruinosa pharmacological and biochemical actions of macrophages in inflammation has not been clearly elucidated. We examined how the methanol extract of C. pruinosa regulates production of IL-1beta, TNF-alpha, nitric oxide (NO), and prostaglandin E(2) (PGE(2)) in vitro and in vivo. The extract inhibits these inflammatory mediators in LPS-stimulated murine macrophage cell line RAW264.7 and primary macrophages, by suppressing gene expression of IL-1beta, TNF-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. Moreover, the extract suppresses the nuclear transcription factor NF-kappaB activation in LPS-stimulated RAW264.7 cells. Administration of the extract significantly decreases the plasma levels of these inflammatory mediators in LPS-injected mice. These results suggest that the C. pruinosa methanol extract suppresses inflammation through suppression of NF-kappaB-dependent inflammatory gene expression, suggesting that the C. pruinosa extract may be beneficial for treatment of endotoxin shock or sepsis.

Animals↗

PubMed2003

Nitric oxide priming protects nitric oxide-mediated apoptosis via heme oxygenase-1 induction.

The role of nitric oxide (NO) as a cytotoxic effector molecule of the immune system is clearly established, but recent studies demonstrate cytoprotective functions of NO at low nontoxic concentrations. However, the mechanism of cytoprotection has not been defined completely. Thus, we investigate the involvement of heme oxygenase-1 (HO-1) in the cytoprotective effects of NO. Exposure of L929 cells to sodium nitroprusside (SNP) resulted in the induction of HO-1 protein expression and heme oxygenase activity. Pretreatment of the cells with a low dose of NO (200 microM SNP) significantly inhibited a high dose of (1000 microM SNP) NO-induced apoptosis in L929 cells. Cytoprotection by a low dose of NO was abrogated in the presence of the heme oxygenase inhibitor zinc protoporphyrin IX. A cytoprotective effect comparable to a low dose of SNP was observed when the cells were transfected with HO-1 gene or preincubated with another HO-1 inducer, hemin. Additional experiments revealed the involvement of carbon monoxide in the cytoprotective effect of SNP/HO-1 in L929 cells. Our results presented here provide evidence to support the essential role of HO-1 in the cytoprotective function of NO priming.

Animals↗

PubMed2003

Identification of novel polymorphisms in the Adam33 gene.

Adam33 is a member of a family of genes that encode membrane-anchored proteins with a disintegrin and a metalloprotease domain and that are primarily expressed in lung fibroblasts and bronchial smooth muscle. The human Adam33 gene is located on chromosome 20p13, a region that has been linked to asthma and bronchial hyperresponsiveness. Recently, the polymorphisms in Adam33 have been found to be associated with asthma. In this study, we performed polymorphism scanning of the entire genomic region, including the promoter region of Adam33, by direct sequencing. We identified 16 novel polymorphisms in the Adam33 gene. Among these novel polymorphisms, three polymorphisms (-2154G-->A, -753T-->A, and -330C-->T) were found to be in the promoter region and one polymorphism (13491 G-->A) was located in 3' untranslated region of the Adam33 gene.

3' Untranslated Regions↗

PubMed2003

Pentoxifylline protects L929 fibroblasts from TNF-alpha toxicity via the induction of heme oxygenase-1.

Tumor necrosis factor-alpha (TNF-alpha) is recognized as a principal mediator of a variety of inflammatory conditions. Pentoxifylline (PTX), which can inhibit cellular TNF-alpha synthesis, also attenuates the toxic effect of TNF-alpha. However, the mechanism underlying PTX-induced cytoprotection is unknown. Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into biliverdin, free iron, and carbon monoxide (CO). This enzyme has recently been shown to have anti-inflammatory and cytoprotective effects. In this study, we investigated whether protection by PTX against TNF-alpha-mediated toxicity could be related to its ability to induce HO-1 expression and HO activity in L929 cells. PTX in the range of 0.1-1.0mM significantly induced HO-1 expression and the resulting HO activity. Pre-incubation of L929 cells with either PTX or the HO activator hemin resulted in the protection of the cells against TNF-alpha-mediated toxicity. Zinc protoporphyrin, a specific HO competitive inhibitor, abrogated the protective effect of PTX. Hemoglobin, a scavenger of CO, reversed the protective effect of PTX. A cytoprotection comparable to PTX was observed when the cells were treated with the CO-releasing compound tricarbonyldichlororuthenium(II) dimer. These results suggest that HO-1 expression and the ensuing formation of the HO metabolite CO may be a novel pathway by which PTX protects L929 cells from TNF-alpha-mediated toxicity.

Blotting, Western↗

PubMed2003

Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages.

Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress, we questioned whether soluble factor from tumor cells induces HO-1 through NO-dependent mechanism in macrophages. We designated this factor as a tumor-derived macrophage-activating factor (TMAF), because of its ability to activate macrophages to induce iNOS. Although TMAF alone showed modest activity, TMAF in combination with IFN-gamma significantly induced iNOS expression and NO synthesis. Simultaneously, TMAF induced HO-1 and this induction was slightly augmented by IFN-gamma. Surprisingly, however, induction of HO-1 by TMAF was not inhibited by the treatment with the highly selective iNOS inhibitor, 1400 W, indicating that TMAF induces the HO-1 enzyme by a NO-independent mechanism. While rIFN-gamma alone induced iNOS, it had no effect on HO-1 induction by itself. Collectively, the current study reveals that soluble factor from tumor target cells induces HO-1 enzyme in macrophages. However, overall biological significance of this phenomenon remains to be determined.

Animals↗

PubMed2003

Four glycosides from the leaves of Abeliophyllum distichum with inhibitory effects on angiotensin converting enzyme.

The bioassay-guided fractionation of the n-BuOH extract of Abeliophyllum distichum afforded acteoside (1), isoacteoside (2), rutin (3), and hirsutrin (4). Compounds 1-3 moderately inhibited the angiotensin I converting enzyme activity in a dose-dependent manner. Compounds 1-3 showed the 50% inhibitory concentration values of 228 micro g/mL, 290 micro g/mL, and 278 micro g/mL, respectively.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Molecular variations in the promoter and coding regions of human Tim-1 gene and their association in Koreans with asthma.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, was considered as a membrane protein that is associated with the development of helper T cell (Th2) biased immune responses, and may be selectively expressed on Th2 cells. In the present study we performed single nucleotide polymorphism (SNP) scanning of the coding and promoter regions of human Tim-1 gene. We identified a total of ten SNPs including five novel SNPs (-1166C>G, -416G>C, -232A>G, 5365C>T, and 5529A>G) in the coding and promoter regions, one novel variation site (-2278_-2276dupATT) in the promoter region and three variations (5383_5397del, 5387_5389insAAC, and 5509_5511delCAA) in exon 4 of human Tim-1 gene. Our results suggest that the exon 4 variation site in human Tim-1 gene is associated with the susceptibility of allergic disease.

Asthma↗

PubMed2003

The absolute configuration of prunioside A from Spiraea prunifolia and biological activities of related compounds.

The stereochemistry of prunioside A isolated from Spiraea prunifolia was determined by chemical transformations and NMR spectral data analysis. The configurations at C-5 and C-6 were determined to be 5S and 6R by application of the modified Mosher's method, CD analysis, and 13C NMR spectroscopic data analysis of an acetonide derivative. Other compounds related to prunioside A have inhibitory effects on the synthesis of nitric oxide in LPS-stimulated macrophage-like RAW 264.7 cells.

Animals↗

PubMed2003

Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8 and macrophage chemoattractant protein-1 secretions in U937 cells.

In an effort to elucidate the mechanism of the anti-inflammatory effect of mudanpi, the root cortex of Paeonia suffruticosa Andrews (Ranunculaceae), we determined the effects of the methanolic extract of mudanpi (MEM) on the secretions of interleukin (IL)-8, a major mediator of acute neutrophil-mediated inflammation, and macrophage chemoattractant protein (MCP)-1, a major mediator of chronic macrophage-mediated inflammation, in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA). MEM significantly inhibited PMA-induced secretions of IL-8 and MCP-1 proteins in a dose-dependent manner. The inhibition of these chemokines by MEM was due to its suppression of IL-8 and MCP-1 genes. In addition, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, one of major constituents isolated from MEM, inhibited PMA-induced secretions of IL-8 and MCP-1 proteins by its suppression of IL-8 and MCP-1 genes. Thus, one possible anti-inflammatory mechanism of mudanpi, an anti-inflammatory Chinese crude drug, may be to inhibit the secretions of inflammatory chemokines.

Anti-Inflammatory Agents↗

PubMed2003

Nitric oxide-mediated cytoprotection of hepatocytes from glucose deprivation-induced cytotoxicity: involvement of heme oxygenase-1.

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme catabolism, which leads to the generation of carbon monoxide (CO), biliverdin, and free iron. One of 3 mammalian HO isoforms, HO-1, is a stress-responsive protein and known to modulate such cellular functions as cytokine production, cell proliferation, and apoptosis to protect organs and tissues from acute injury. Although nitric oxide (NO)-mediated cytoprotective effects against cytotoxicity induced by glucose deprivation have been well recognized, the underlying mechanisms remain to be elucidated. Thus, we investigate the involvement of HO-1 in the cytoprotective effects of NO. Deprivation of glucose markedly reduced the viability of BNL CL.2 cells and primary rat hepatocytes. Pretreatment with NO donor, sodium nitroprusside (SNP), protected hepatocytes from glucose deprivation-induced cytotoxicity; zinc protoporphyrin (ZnPP) IX, an inhibitor of HO, was found to block the SNP-induced cytoprotection. SNP increased the induction of HO-1 protein as well as its activity in hepatocytes. A cytoprotective effect comparable to SNP was observed when the cells were transfected with HO-1 gene or preincubated with another HO-1 inducer, hemin. Additional experiments revealed the involvement of CO in the cytoprotective effect of SNP/HO-1 in BNL CL.2 cells. CO mediated cytoprotective effect through suppression of ERK MAPK activation. In conclusion, our results show that SNP protects hepatocytes from glucose deprivation-induced cytotoxicity through up-regulation of HO-1. Thus, HO-1 might be an important cellular target of NO donor with clinical implications for the prevention of acute liver injury in several pathological conditions.

Animals↗

PubMed2003

Soluble factor from murine bladder tumor-2 cell elevates nitric oxide production in macrophages and enhances the taxol-mediated macrophage cytotoxicity on tumor cells.

The therapeutic mechanism of taxol is believed to reside primarily in its ability to stabilize microtubules and prevent cell progression through mitosis. Taxol also can activate macrophage-mediated antitumor mechanism through a nitric oxide (NO)-dependent pathway. To address whether any mechanisms account for superficial urinary bladder tumor cell killing, we evaluated the effects of taxol on the growth and viability of murine bladder tumor-2 (MBT-2) cells in vitro, both in the absence and presence of murine macrophages. In addition, we evaluated whether a soluble factor generated from MBT-2 cells could modulate the antitumor activity of the taxol-activated macrophages. Although taxol inhibited the growth of MBT-2 cells, it did not kill the tumor cells. However, preincubation of macrophages with taxol significantly decreased the viability of MBT-2 cells. Secretion of NO correlated with MBT-2 cell killing, and the activated macrophages failed to kill tumor cell targets in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase. By the co-culture of macrophages and MBT-2 cells, untreated macrophages also released modest amount of NO and this was synergistically augmented by the treatment with taxol, indicating that MBT-2 tumor cells released some unknown factor that activated the macrophages and enhanced NO production. We named this factor the tumor-derived macrophage activating factor (TMAF). The TMAF-mediated activation of macrophages to enhance the NO production was not blocked by treatment of macrophages with oxidized low-density lipoprotein (Ox-LDL), implying that the scavenger receptor of macrophages is not involved. Sodium nitroprusside (SNP), an NO donor given to the MBT-2 cells, increased the activities of c-Jun N-terminal kinase and caspase-3 in MBT-2 cells and associated with nucleosomal fragmentation or apoptosis, whereas taxol had no direct effect on these parameters. Collectively, our results strongly suggest that taxol kills the murine bladder tumor cells through indirect activation of macrophages via NO-dependent apoptosis, instead of its better-known role as the direct antimitotic action. Our results further demonstrate that TMAF acts in synergy with taxol to activate the macrophages to elicit enhanced tumor cell killing ability.

Animals↗

PubMed2003

Nitric oxide prevents 6-hydroxydopamine-induced apoptosis in PC12 cells through cGMP-dependent PI3 kinase/Akt activation.

Nitric oxide (NO) functions not only as an important signaling molecule in the brain by producing cGMP, but also regulates neuronal cell apoptosis. The mechanism by which NO regulates apoptosis is unclear. In this study, we demonstrated that NO, produced either from the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) or by transfection of neuronal NO synthase, suppressed 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells by inhibiting mitochondrial cytochrome c release, caspase-3 and -9 activation, and DNA fragmentation. This protection was significantly reversed by the soluble guanylyl cyclase inhibitor 1H-(1,2,4)-oxadiazole[4,3-a]quinoxalon-1-one, indicating that cGMP is a key mediator in NO-mediated anti-apoptosis. Moreover, the membrane-permeable cGMP analog 8-Br-cGMP inhibited 6-OHDA-induced apoptosis. These anti-apoptotic effects of SNAP and 8-Br-cGMP were suppressed by cGMP-dependent protein kinase G (PKG) inhibitor KT5823, indicating that PKG is a downstream signal mediator in the suppression of apoptosis by NO and cGMP. Both SNAP and 8-Br-cGMP induced endogenous Akt activation and Bad phosphorylation, resulting in the inhibition of Bad translocation to mitochondria; these effects were inhibited by KT5823 and the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and Wortmannin. Our data suggest that the NO/cGMP pathway suppresses 6-OHDA-induced PC12 cell apoptosis by suppressing the mitochondrial apoptosis signal via PKG/PI3K/Akt-dependent Bad phosphorylation.

Anilides↗

PubMed2003

Effects of Qigong on immune cells.

The aim of this study was to investigate the influence of two acute Qigong interventions (Qi-training and Qi-therapy) on immune cells. The Qigong interventions were compared with placebo training and placebo therapy in which no attempt was made to gather or move Qi. Immune cell numbers were measured pre-intervention, immediately post-intervention and 1 or 2 hours post-intervention. White blood cells increased significantly 2 hours after actual Qi-training (p < 0.05) but not sham training compared with pre-intervention There were significant increases in lymphocytes 2 hours after actual but not sham Qi-training (p < 0.05) and monocyte numbers were significantly increased immediately after both actual Qi-training (p < 0.01) and sham training (p < 0.05). NK cell numbers decreased significantly both immediately after Qi-training and after sham movements done without concomitant Qi-training (p < 0.01). There were no significant effects on neutrophils. Actual Qi-therapy but not sham therapy increased monocyte numbers immediately after Qi-therapy, and lymphocytes increased more after real than after sham therapy. Neutrophils were again little changed The data indicate that a single Qigong intervention can increase the monocyte and lymphocyte numbers.

Breathing Exercises↗

PubMed2003

Effects of Qigong on blood pressure, blood pressure determinants and ventilatory function in middle-aged patients with essential hypertension.

This study was designed to measure changes in blood pressure (BP), urinary catecholamines and ventilatory functions of patients with mild essential hypertension after 10 weeks of Qigong (Shuxinpingxuegong). Fifty-eight patients volunteered to participate in this study and were randomly divided into either a Qigong group (n = 29), or a control group (n = 29). Systolic blood pressure and diastolic blood pressure decreased significantly in the Qigong group such that both became significantly lower after 10 weeks in the Qigong than in the control group. Also, there was a significant reduction of norepinephrine, metanephrine and epinephrine compared to baseline values in the Qigong group. The ventilatory functions, forced vital capacity and forced expiratory volume per sec, were increased in the Qigong group but not the control. These results suggest that Qigong may stabilize the sympathetic nervous system is effective in modulating levels of urinary catecholamines and BP positively, and in improving ventilatory functions in mildly hypertensive middle-aged patients.

Analysis of Variance↗