[Show abstract][Hide abstract] ABSTRACT: It is well known that endocrine disruptors (EDs) act as anti-estrogenic agents and affect the function of reproductive organ. EDs are also thought to affect thyroid hormone (TH) system which is important for biological functions such as growth, development and metabolism. However, it is still not clear how EDs are able to regulate TH receptor (TR)-mediated functions. In this study, therefore, the modulatory effects of representative EDs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (Aroclor 1254) and bisphenol A (BPA) were examined using TR-expressing GH3 cells (a rat pituitary gland epithelial tumor cell line) activated by triiodothyronine (T3). EDs tested significantly blocked T3 binding to TR in a dose-dependent manner. Biochemical characterization by Scatchard and Lineweaver-Burk plot analyses indicated that TCDD and aroclor 1254 bound to TH receptors in a competitive inhibitory manner, whereas BPA bound to TH receptors in a non-competitive pattern. The different inhibitory mode of action by EDs was also found in regulating TR-mediated production of prolactin (PRL). Aroclor 1254 exposure for 48 h enhanced T3-mediated PRL production, but BPA down-regulated. These results suggest that the EDs (TCDD, Aroclor 1254 and BPA) could differentially bind to TR and distinctly regulate the action of TR function, even though EDs are structurally similar.
Archives of Pharmacal Research 06/2007; 30(5):616-23. DOI:10.1007/BF02977657 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the modulatory effect of curcumin on the functional activation of primary microglial cells, brain mononuclear phagocytes causing the neuronal damage, largely remains unknown. The current study examined whether curcumin influenced NO production in rat primary microglia and investigated its underlying signaling pathways. Curcumin decreased NO production in LPS-stimulated microglial cells in a dose-dependent manner, with an IC(50) value of 3.7 microM. It also suppressed both mRNA and protein levels of inducible nitric oxide synthase (iNOS), indicating that this drug may affect iNOS gene expression process. Indeed, curcumin altered biochemical patterns induced by LPS such as phosphorylation of all mitogen-activated protein kinases (MAPKs), and DNA binding activities of nuclear factor-kappaB (NF-kappaB) and activator protein (AP)-1, assessed by reporter gene assay. By analysis of inhibitory features of specific MAPK inhibitors, a series of signaling cascades including c-Jun N-terminal kinase (JNK), p38 and NF-kappaB was found to play a critical role in curcumin-mediated NO inhibition in microglial cells. The current results suggest that curcumin is a promising agent for the prevention and treatment of both NO and microglial cell-mediated neurodegenerative disorders.
Life Sciences 11/2006; 79(21):2022-31. DOI:10.1016/j.lfs.2006.06.048 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our present study, a shrinkage anomaly present during sintering in an anatase powder compact was examined. It was observed that the shrinkage stagnates during sintering. This anomaly has been investigated using dilatometry, X-ray powder diffraction, and scanning electron microscopy. Quantitative phase analysis using X-ray diffraction revealed that the shrinkage anomaly is correlated to the phase transition from anatase to rutile. A calculation based on specific volumes of anatase and rutile showed that the phase transition generated 8.6% additional porosity in the anatase powder compact and this retards the densification as well as the shrinkage in the anatase sample. Microstructural observation of anatase and rutile samples having the same shrinkage confirmed this result.
Journal of the American Ceramic Society 01/2005; 81(6):1692 - 1694. DOI:10.1111/j.1151-2916.1998.tb02536.x · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several commercial silver electrode pastes have been evaluated for use with BiNbO4-based low-firing ceramics. After electrode application and subsequent cofiring, the electrode pattern on the ceramic was no longer visible. A bismuth-rich second phase was present at the electrode/BiNbO4 interface, and silver was detected in the second phase. Systematic X-ray diffractometry analysis of the mixtures between different silver pastes and doped/undoped BiNbO4 revealed an interaction between the silver and the BiNbO4. This reaction was responsible for the disappearance of the silver electrode patterns.
Journal of the American Ceramic Society 01/2005; 81(11):3038 - 3040. DOI:10.1111/j.1151-2916.1998.tb02737.x · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The bioassay-directed isolation of a marine brown alga, Ecklonia cava, afforded four phlorotannin derivatives, eckol (1), 8,8'-bieckol (2), 8,4"'-dieckol (3), and phlorofucofuroeckol A (4). Among these compounds, 2 and 3 exhibited an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease. Specifically, they inhibited the RT more potently than the protease. The inhibitory activity of compound 2 (IC(50), 0.51 microM) against HIV-1 RT was comparable to that of nevirapine (IC(50), 0.28 microM), a reference compound. An enzyme kinetic assay showed that this compound inhibited the RNA-dependent DNA synthesis activity of HIV-1 RT noncompetitively against dUTP/dTTP with a K(i) value of 0.78 microM. With respect to the homopolymeric template/primer, (rA)n(dT)15, 8,8'-bieckol (2) displayed an uncompetitive type of inhibition (K(i), 0.23 microM).
[Show abstract][Hide abstract] ABSTRACT: Forty-seven species of marine macroalgae from the coast of Korea havebeen screened for the presence of inhibitory compounds against humanimmunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and HIV-1integrase (IN). One of 4 Chlorophyta, 8 of 17 Phaeophyta and 6 of 26 Rhodophytashowed inhibitory activity against HIV-1 reverse transcriptase. Five species(Ecklonia cava, Ishige okamurae,Sargassum confusum, Sargassumhemiphyllum, Sargassum ringgoldianum) belongingto Phaeophyta showed to inhibit the 3-processing activity of HIV-1integrase. In cell-based assays, the methanol extracts ofBossiella sp. and Chondriacrassicaulis inhibited cytopathogenecity of HIV-1 at a concentrationbelow that cytotoxic for MT4 cells.
[Show abstract][Hide abstract] ABSTRACT: The bioassay-directed isolation of Terminalia chebula fruits afforded four human immunodeficiency virus type 1 (HIV-1) integrase inhibitors, gallic acid ( 1) and three galloyl glucoses ( 2 - 4). In addition, four flavonol glycoside gallates ( 5 - 8) from Euphorbia pekinensis containing the galloyl moiety also showed the inhibitory activity at a level comparable to those of 2 - 4. By comparison with the activities of the compounds not bearing this moiety, it is proposed that the galloyl moiety plays a major role for inhibition against the 3'-processing of HIV-1 integrase of these compounds.
[Show abstract][Hide abstract] ABSTRACT: Elevated p21ras expression is associated with tumor aggressiveness in breast cancer including the extent of invasion into fat tissues, infiltration into lymphatic vessels and tumor recurrence. In the present study, we have examined the roles of H-ras and N-ras, members of the human ras gene family, in the pathogenesis of breast cancer. We show that H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells (MCF10A) as determined by the Matrigel invasion assay, whereas both H-ras and N-ras induce anchorage-independent growth, as shown by soft agar assay. We examined the effects of H-ras and N-ras activation on the expression of MMP-2 and MMP-9, which can degrade type IV collagen, the major structural collagen of the basement membrane. We show that MMP-2 is efficiently induced by H-ras, whereas MMP-9 induction is more prominent in N-ras-activated MCF10A cells. We also show that H-ras-mediated invasiveness is significantly inhibited when the expression of MMP-2 is down-regulated, using an oligodeoxyribonucleotide complementary to the MMP-2 mRNA, or when MMP-2 activity is blocked by its inhibitor TIMP-2 (tissue inhibitors of matrix metalloproteinase-2). Our results show that the H-ras-induced invasive phenotype is associated more closely with the expression of MMP-2 in human breast epithelial cells, rather than the induction of MMP-9 expression, as shown previously for rat embryonic fibroblasts.
International Journal of Cancer 02/2000; 85(2):176-81. DOI:10.1002/(SICI)1097-0215(20000115)85:2<176::AID-IJC5>3.0.CO;2-E · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7,12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea (5x10(-3) M) was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from 1x10(-6) M to 5x10(-4) M did not significantly inhibit unscheduled DNA synthesis induced by either MMS (1x10(-4) M) or EMS (1x10(-2) M). In contrast, DHEA significantly inhibited unscheduled DNA synthesis induced by BaP (6.5x10(-5) M) and DMBA (2x10(-5) M). DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the solvent control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.
Archives of Pharmacal Research 11/1999; 22(5):474-8. DOI:10.1007/BF02979155 · 2.05 Impact Factor