Biomedical subjects

H J Chae

Publications and source records attributed to H J Chae.

At least 19 recordsLinked to original sources

PubMed2006

Placenta hominis protects osteoporosis in ovariectomized rats.

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.

Animals↗

PubMed2005

Carbon monoxide and nitric oxide protect against tumor necrosis factor-alpha-induced apoptosis in osteoblasts: HO-1 is necessary to mediate the protection.

BACKGROUND: Carbon monoxide (CO) and nitric oxide (NO) each have unique roles for various inflammatory states, including inflammatory bone resorption. Although it is known that NO can induce the expression of the cytoprotective enzyme HO-1, there is no information as to whether the protective effect of CO requires NO production or whether CO must induce the expression of HO-1 to exert its functional effects. METHODS: Murine osteoblast cells, MC3T3E1 osteoblasts, were cultured for CO and NO-associated HO-1 experiments and were transfected with pcDNA 3, pcDNA 3-HO-1, control siRNA or HO-1 siRNA using Nucleofector. For cell death measurement, MTT and annexin V assays were used. We performed Western blotting to check the expressions of HO-1 and iNOs and measured the HO-1 enzyme activity. We also measured the amounts of nitrite and nitrate using Griess reagents. RESULTS: The increased expression of HO-1 is required for the protective effect of NO and a single treatment of CO can increase the expression of HO-1, and this is also important for the protective effect of CO in MC3T3E1 osteoblasts. CO as well as NO attenuates the TNF-alpha-induced apoptosis in osteoblasts. The anti-apoptotic effect of CO or NO is not mediated by cGMP, and CO has no effect on the release of NO. The inhibition of HO-1 with using the HO-1 inhibitor ZnPP or HO-1 siRNA resulted in a striking increase of apoptosis in the CO/TNF-alpha-treated cells. Furthermore, HO-1 overexpression showed resistance against the TNF-alpha-induced cytotoxicity in the MC3T3E1 osteoblasts. CONCLUSIONS: There is a need for HO-1 expression to mediate the protection provided by exogenous CO or NO in osteoblasts.

3T3 Cells↗

PubMed2005

p38 MAPK and NF-kappaB on IL-6 release in human gingival fibroblasts.

The induction of interleukin-6 (IL-6) using a proinflammatory cytokine (IL-1beta) was studied in human gingival fibroblasts (HGFs) in relation to p38 MAPK and NF-kappaB transcription factor. When added to HGFs, IL-1beta had a stimulatory effect on the production of IL-6, and this effect was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release also was reduced by the addition of pyrrolidine dithiocarbamate or NF-kappaB SN50, which has been reported as potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had more inhibitory effect on IL-6 release. IL-13 stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on the NF-kappaB activation, and both the NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the IL-1beta-stimulated HGFs. These results strongly suggest that both p38 MAPK and NF-kappaB are required in IL-1beta-induced IL-6 synthesis and that these two IL-1beta-activated pathways can be primarily dissociated.

Dose-Response Relationship, Drug↗

PubMed2004

Prevention of bone loss in ovariectomized rats: the effect of Salvia miltiorrhiza extracts.

The preventive effect of Salvia miltiorrhiza extracts (SMEs) on the progress of bone loss induced by ovariectomy (OVX) was studied in rats. We measured body weight and bone histomorphometry in sham, OVX or SMEs-administered OVX rats. From light microscopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in OVX rats, whereas those of the same bone in sham rats and in SMEs-administered rats were composed of fine particles. The trabecular bone area and trabecular thickness in OVX rats decreased by 50% from those in sham rats, these decreases were completely inhibited by administration of SMEs for 7 weeks. In this study, the mechanical strength in femur neck was significantly enhanced by the treatment of SMEs for 7 weeks. In OVX rats, free T3 was normal in all cases, whereas free T4 was significantly increased. Although there was no difference between OVX and SMEs-administered rats in T3 level, we have found significant difference between them in T4 level. These results strongly suggest that SMEs are effective in preventing the development of bone loss induced by OVX in rats.

Alkaline Phosphatase↗

PubMed2004

Yuk-Hap-Tang induces apoptosis by intervening mn-SOD in human cervical carcinoma HeLa cells.

Yuk-Hap-Tang (YHT) induces cell death in human cervical carcinoma HeLa cells. Caspase-3, -6 and -9 were markedly activated in HeLa cells treated with YHT. The preferred substrate for caspase-3 cysteine protease, PARP, was cleaved to its 85-kDa cleavage product. YHT increased the amount of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. Although p53 has been reported to accumulate in cancer cells in response to anticancer agents, the p53 expression level was not changed in HeLa cells treated with YHT. Manganese (Mn)-TBAP, a mitochondria-specific SOD mimetic agent and NAC/GSH (N-acetyl cysteine/ reduced glutathione) reduced the YHT-induced cytotoxicity and decreased the number of the YHT-induced apoptotic cells. Furthermore, YHT reduced the expression of Mn-SOD protein and its activity in HeLa cells. The data demonstrate that YHT induces the apoptosis of human cervical carcinoma HeLa cells by intervening Mn-SOD.

Antioxidants↗

PubMed2002

Inhibition of tumour necrosis factor-alpha secretion from rat astrocytes by Sesim-Tang.

Substance P (SP) can stimulate secretion of tumour necrosis factor-alpha (TNF-alpha) from astrocytes stimulated with lipopolysaccharide (LPS). In this study, we have examined whether an aqueous extract of Sesim-Tang inhibits the secretion of TNF-alpha from primary cultures of rat astrocytes. Sesim-Tang (10-1000 microg/mL) significantly inhibited the TNF-alpha secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by Sesim-Tang. Treatment with Sesim-Tang (10-1000 microg/mL) of astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in astrocytes was progressively inhibited with increasing amounts of IL-1 neutralizing antibody. Our results suggest that Sesim-Tang may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that Sesim-Tang has an antiinflammatory activity in the central nervous system.

Animals↗

PubMed2002

ERK MAP Kinase is required in 1,25(OH)2D3-induced differentiation in human osteoblasts.

Expression of alkaline phosphatase(ALP)activity represents a key event during the differentiation processes of osteoblasts, and the level of ALP activity has been routinely used as a relative measure of differentiation stages of osteoblasts. In human osteoblasts, we showed that vitamin D3 analogue, 1,25(OH)2D3, had a stimulatory effect on ALP activity after 3 days, compared with control. The treatment of PD098059, an ERK MAP Kinase inhibitor, had a reducing effect on ALP activity, a differentiation marker in 1,25(OH)2D3-treated primary human osteoblasts. However, SB203580, a potent p38 MAP Kinase inhibitor, had no effect on the differentiation in this system. This indicates that ERK, not p38, is directly related to 1,25(OH)2D3-stimulated ALP activity in primary human osteoblasts. These results also show that the vitamin D3 analogue stimulates ERK1 activation in primary human osteoblasts. This finding provides one of signaling pathways for differentiation in primary human osteoblasts.

Alkaline Phosphatase↗

PubMed2001

Antiosteoporotic activity of Dae-Bo-Won-Chun in ovariectomized rats.

The preventive effect of the herbal formulation, "Dae-Bo-Won-Chun" (DBWC), on the progress of bone loss induced by ovariectomy (OVX) was studied in rats. From light microscope analyses, porous or erosive appearances were observed on the surface of trabecular bone of tibia in ovariectomized rats, whereas those of the same bone in sham-operated rats were composed of fine particles. The trabecular bone area and trabecular thickness in ovariectomized rats decreased by 50% from those in sham-operated rats, these decreases were completely inhibited by administration of DBWC at a concentration of 10 mg/kg per day for 7 weeks. The mechanical strength of the neck of the femur was decreased by ovariectomy, and this was significantly suppressed by the administration of DBWC. Serum phosphorus, alkaline phosphatase and thyroxine levels in ovariectomized rats increased compared with those in sham-operated rats, and increases were completely inhibited by the administration of DBWC. These results strongly suggest that DBWC is effective in preventing the development of bone loss induced by ovariectomy in rats.

Animals↗

PubMed2001

Inhibitory effect on immunoglobulin E production in vivo and in vitro by Siegesbeckia glabrescens.

Elevated levels of immunoglobulin (Ig)E are associated with immediate-type allergic reactions. The effect of an aqueous extract of Siegesbeckia glabrescens (Compositae) whole plants (SGWP) on in vivo and in vitro IgE production was studied in mice. SGWP dose-dependently inhibited the active systemic anaphylaxis and serum IgE production induced by immunization with ovalbumin and Bordetella pertussis toxin absorbed to aluminium hydroxide gel. SGWP dose-dependently inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, SGWP also showed an inhibitory effect on IgE production. These results suggest that SGWP has an anti-allergic activity by inhibiting IgE production from B cells.

Anaphylaxis↗

PubMed2001

Blockade of the p38 mitogen-activated protein kinase pathway inhibits inducible nitric oxide synthase and interleukin-6 expression in MC3T3E-1 osteoblasts.

Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6. However IFN- gamma, LPS and TNF- alpha individually induces non-detectable or small amounts of NO and IL-6 in MC3T3E-1 osteoblasts. The role of mitogen-activated protein kinase (MAPK) activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580), are significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p38 MAPK pathway controlled iNOS and IL-6 transcription levels. These data suggest that p38 MAPK plays an important role in the secretion of NO and IL-6 in LPS/IFN- gamma or TNF- alpha /IFN- gamma -treated MC3T3E-1 osteoblasts.

Animals↗

PubMed2001

Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic reactions by water extract of white eggplant (Solanum melongena).

We investigated the effect of water extract of Solanum melongena(SMWE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. Oral administration of SMWE (1 g kg(-1)) completely inhibited compound 48/80-induced anaphylactic reaction. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Oral administration of SMWE (0.01--1 g kg(-1)) significantly inhibited passive cutaneous anaphylactic reaction activated by anti-DNP IgE to between 83.10 +/- 1.67% and 70.17 +/- 2.17%. SMWE (0.01--1 mg ml(-1)) also inhibited histamine release activated by compound 48/80 to between 93 +/- 2.65 and 70 +/- 1.50%. Moreover, SMWE (0.01--1 mg ml(-1)) had a significant inhibitory effect on IgE-induced tumor necrosis factor (TNF)-alpha secretion from rat peritoneal mast cells. These results indicate that SMWE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha secretion from mast cells.

Administration, Oral↗

PubMed2001

Utilization of brewer's yeast cells for the production of food-grade yeast extract. Part 1: Effects of different enzymatic treatments on solid and protein recovery and flavor characteristics.

Yeast extract was produced from brewer's yeast of a beer factory by combined enzymatic treatments using endoprotease, exoprotease, 5'-phosphodiesterase, and adenosine monophosphate (AMP)-deaminase. Effects of enzyme combination, enzyme dosages and treatment sequence on the recovery of solid and protein, flavor and compositional characteristics were investigated. Exoprotease dosage strongly affected the recovery of protein and degree of hydrolysis (DH) and sensory characteristics. When the yeast cells were treated using optimal combination of endoprotease and exoprotease (0.6% Protamex and 0.6% Flavourzyme), high solid recovery (48.3-53.1%) and the best flavor profile were obtained. Among various treatment sequences using multiple enzymes, treatment with protease followed by nuclease resulted in the highest 5'-guanosine monophosphate (5'-GMP) content. The optimal concentrations of both 5'-phosphodiesterase and AMP-deaminase were found to be 0.03%. After treatments using optimal combination of enzyme, enzyme dosages and treatment sequence for four enzymes, a high solid yield of 55.1% and 5'-nucleotides content of 3.67% were obtained.

AMP Deaminase↗

PubMed2001

Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner.

Sodium nitroprusside (SNP) induces apoptosis in H9C2 cardiac muscle cells. Treatment with an exogenous NO donor SNP (2 mM) to H9C2 cells resulted in apoptotic morphological changes; a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activity of caspase-3 like protease was increased during SNP-induced cell death. However, the activity of caspase-1 like protease was not affected by SNP. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the SNP-induced cell death. SNP markedly activated three MAP kinases (JNK/SAPK, ERK and p38 MAP kinase) in the cardiac muscle cells. In this study, selective inhibition of the ERK or p38 MAPK pathway (by PD98059 or SB203580, respectively) had no effect on the extent of SNP-induced apoptosis in cardiac muscle cells. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK will be related to SNP-induced apoptosis of H9C2 cardiac muscle cells.

Amino Acid Chloromethyl Ketones↗

PubMed2001

The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts.

The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor necrosis factor-alpha), was studied in a human osteoblast cell line (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB transcription factor. When added to MG-63 cells, tumor necrosis factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which has been reported to be a potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-alpha stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha-induced NF-kappaB activation and both NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the TNF-alpha-stimulated osteoblasts. In addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.

Antioxidants↗

PubMed2001

Hypoxia induces apoptosis by caspase activation accompanying cytochrome C release from mitochondria in MC3T3E1 osteoblasts. p38 MAPK is related in hypoxia-induced apoptosis.

The aim of this study is to elucidate the possible mechanism of apoptosis in response to hypoxia in MC3T3E1 osteoblasts. MC3T3E1 osteoblasts under hypoxic conditions (2% oxygen) resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay and nuclear morphologystained with fluorescent dye, Hoechst 33258. Pretreatment with Z-VAD-FMK, a pan-caspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to hypoxia. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase- activity (YVADase) was detected. To confirm what caspases are involved in apoptosis, western blot analysis was performed using anti-caspase-3 or -6 antibody. The 10-kDa protein, corresponding to the active products of caspase-3 and the 10-kDA protein of the active protein of caspase-6 were generated in hypoxia-challenged cells in which processing of the full length form of caspase-3 and -6 was evident. With a time course similar to this caspase-3 and -6 activation was evident, hypoxic stress caused the cleavage of lamin A, typical of caspase-6 activity. In addition, the stress elicited the release of cytochrome c into the cytosol during apoptosis. Furthermore, we have observed that pre-treatment with SB203580, a selective p38 MAP kinase (p38 MAPK) inhibitor, attenuated the hypoxia-induced apoptosis. The addition of SB203580 suppressed caspase-3 and -6-like protease activity by hypoxia up to 50%. In contrast, PD98059 had no effect on the hypoxia-induced apoptosis. To confirm the involvement of MAP kinase, JNK/SAPK, ERK, or p38 kinase assay was performed. Although p38 MAPK was activated in response to hypoxic treatment, the other MAP kinase -JNK/SAPK or ERK- was not or modestly activated. These results suggest that p38 MAPK positively regulates hypoxia-induced apoptosis in MC3T3E1 osteoblasts.

3T3 Cells↗

PubMed2001

Kunbi-Boshin-Hangam-Tang stimulates nitic oxide production through activation of nuclear factor-kappaB.

The objective of the currently study was to determine the effect of Kunbi-Boshin-Hangam-Tang (KBH-Tang) on the production of nitric oxide (NO). Stimulation of RAW 264.7 cells with KBH-Tang after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in increased NO synthesis. KBH-Tang partially increased NO synthesis by itself. When KBH-Tang was used in combination with rIFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) protein. NO production was inhibited by NG-monomethyl-L-arginine (NGMMA). Furthermore, activation of nuclear factor (NF)-kappaB was increased by KBH-Tang. These results suggest that KBH-Tang may stimulate the NO production through the activation of the NF-kappaB.

Animals↗

PubMed2001

Signal transduction of nitric oxide donor-induced protection in hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblasts.

Nitric oxide (NO) attenuates hydrogen peroxide (H2O2)-mediated injury to H9C2 cardiomyoblasts. To examine the role of nitric oxide, cultured H9C2 cardiomyoblasts were treated with H2O2 for 2 h in the presence or absence of the NO donor, diethylamine nitric oxide (DEANO). DEANO (30 microM) attenuated H2O2-induced apoptosis in H9C2 cells. H2O2-exposed H9C2 cells resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay, nuclear morphology stained with fluorescent dye, Hoechst 33258 and Annexin V staining. Pretreatment with z-VAD-FMK, a pancaspase inhibitor, or z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to H2O2. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. Treatment of H9C2 cells with 100 microM H2O2, resulted in a strong activation of JNK/SAPK. However, the activation of JNK/ SAPK was clearly attenuated by 30 microM DEANO. Furthermore, the dominant negative JNK and SEK1-expressing cells displayed a marked decrease in a number of apoptotic cells. This inhibition of JNK1 in the system is involved in the protection of H2O2-induced apoptosis in H9C2 cardiomyoblasts.

Animals↗

PubMed2001

Nitric oxide prevents the IFN-gamma/LPS-induced hepatotoxicity in a protein kinase G-independent manner.

Although it has been well known that the role of LPS on hepatotoxicity is mediated through TNF-alpha, the direct cytotoxic effect of LPS on IFN-gamma-primed hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that the IFN-gamma-mediated death of murine embryonic liver BNL CL2 cells is potentiated by LPS (0.5 microg/ml). In addition, an exogenous NO donor, sodium nitroprusside (SNP) significantly prevents cell death induced by IFN-gamma alone or IFN-gamma plus LPS (IFN-gamma/LPS) in a dose-dependent manner over 25 microM. SNP significantly blocked the death of BNL CL2 cells only when it was added within 12 hr after treatment of IFN-gamma and IFN-gamma/LPS. The preventive effect of SNP occurred in parallel with the suppression of caspase 3-like protease activation. We have also demonstrated that a relatively high concentration as well as an appropriate period of exposure to NO may be critical to maintain cell viability from the cytotoxic effect of IFN-gamma and IFN-gamma/LPS. Furthermore, the preventive effect of SNP on IFN-gamma/LPS-induced cell death is mediated by a protein kinase G (PKG)-independent manner.

Animals↗