• 한국동물학회지
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• 제35권2호
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• pp.161-172
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• 1992

In the short-term treahent of 12-0-tetradecanoylphorbol-13-acetate (TPA) or platelet-derived growth factor (PDGF), the'Wh and PDGF induced the Protein Kinase C (PKC) activation and migration from the cytoplasm to the peripheral nulcear membrane. And the activated PKC which was directly or indirectly stimulated by TPA or PDGF Phosphorylated many kinds of PKC's targeting proteins and induces various biological responses. Especially, the cytoplasmic PKC was phosphorylated within 1 hr and 10 min by TPA-and PDGF-treahent respectivelv. In the long-term treatment of TPA or PDGF, both of them induced the down-regulation and translocation of PKC in the mvoblasts. The down-regulation of PKC isozyrnes, the pattern of PKC I and ll was similar to the PKC 111 isozpnes in the cytoplasm. But in the nucleolus, the TPA did not induce and down-regulation or the inhibition of the immunoreactivity of PKC III antibody. This investigation indicates that each isozvmes of PKC mal be performed the different effects to the down-regulation of the cytoplasm or nucleolus. And douvn-regulated myoblasts contained low immunoreactivity of PKC antibodies.

• Nutritional Sciences
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• 제6권1호
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• pp.25-30
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• 2003

The effects of soy-isoflavones, which are phytoestrogens derived from plants with a flavonoid structure, on cyclooxygenase -2 (COX-2) expression, PGE2 production, and mapkinases expression, were investigated in experimentally-induced atherogenic rats by feeding a high fat-high cholesterol diet. Female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were randomized to the following treatments for an eight-week experimental period: 17$\beta$-estradiol (200$\mu$ g/kg diet), low concentration of isoflavones (0.8g/kg diet), and high concentration of isoflavones (4.0g/kg diet). In the group supplemented with a high dose of isoflavones, COX-2 expression was down-regulated. This down-regulation was accompanied by a reduced expression of pERK1/2. In the second experiment using 48-week old female Sprague-Dawly rats, the effects of isoflavones and estrogen were compared in the basal estrogen-supplementation at the level of 600$\mu$ g/kg diet. Isoflavones induced the marked down-regulation of COX-2 protein and the decrease in $PGE_2$ production in estrogen supplemented states and this was followed by the down-regulation of p38 among mapkinases. The two different mapkinases are involved in the down-regulation of COX-2 depending on estrogen-deficient and estrogen supplemented states. This kind of COX-2 down-regulation by isoflavones was not observed in the different tissue, mammary glands. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by isoflavonesin the absence or the presence of estrogen ave required in vivo system of female rats.

• Molecules and Cells
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• 제26권3호
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• pp.285-290
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• 2008

Estrogen-induced proliferation in estrogen receptor (ER)-positive breast cancer cells is primarily mediated through two distinct intracellular receptors, $ER{\alpha}$ and $ER{\beta}$. Although tumor necrosis factor alpha ($TNF{\alpha}$) and $E2/ER{\alpha}$ are known to exert opposing effects on cell proliferation in MCF-7 cells, the mechanism by which $TNF{\alpha}$ antagonizes $E2/ER{\alpha}$-mediated cell proliferation is not well understood. The present study suggests that reduced cell survival in response to $TNF{\alpha}$ treatment in MCF-7 cells may be associated with the down-regulation of $ER{\alpha}$ protein. The decrease in $ER{\alpha}$ protein level was accompanied by an inhibition of $ER{\alpha}$ gene transcription. Cell viability was decreased synergistically by the combined treatment with $ER{\alpha}$-siRNA and $TNF{\alpha}$. Furthermore, pretreatment of cells with the PI3-kinase (PI3K)/ Akt inhibitor, LY294002, markedly enhanced $TNF{\alpha}$-induced down-regulation of the $ER{\alpha}$ protein, suggesting that the PI3K/Akt pathway might be involved in control of the $ER{\alpha}$ level. Moreover, down-regulation of $ER{\alpha}$ by $TNF{\alpha}$ was not inhibited in cells that were pretreated with the proteasome inhibitors, MG132 and MG152, which suggests that proteasome-dependent proteolysis does not significantly influence $TNF{\alpha}$-induced down-regulation of $ER{\alpha}$ protein. In contrast, the effect of the PI3K/Akt inhibitor on $ER{\alpha}$ was blocked in cells that were treated with LY294002 in the presence of the proteasome inhibitors. Collectively, our findings show that the $TNF{\alpha}$ may partly regulate the growth of MCF-7 breast cancer cells through the down-regulation of $ER{\alpha}$ expression, which is primarily mediated by a PI3K/Akt signaling.

• Molecules and Cells
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• 제38권8호
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• pp.705-714
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• 2015

We investigated the role of HDAC3 in anti-cancer drug-resistance. The expression of HDAC3 was decreased in cancer cell lines resistant to anti-cancer drugs such as celastrol and taxol. HDAC3 conferred sensitivity to these anti-cancer drugs. HDAC3 activity was necessary for conferring sensitivity to these anti-cancer drugs. The down-regulation of HDAC3 increased the expression of MDR1 and conferred resistance to anti-cancer drugs. The expression of tubulin ${\beta}3$ was increased in drug-resistant cancer cell lines. ChIP assays showed the binding of HDAC3 to the promoter sequences of tubulin ${\beta}3$ and HDAC6. HDAC6 showed an interaction with tubulin ${\beta}3$. HDAC3 had a negative regulatory role in the expression of tubulin ${\beta}3$ and HDAC6. The down-regulation of HDAC6 decreased the expression of MDR1 and tubulin ${\beta}3$, but did not affect HDAC3 expression. The down-regulation of HDAC6 conferred sensitivity to taxol. The down-regulation of tubulin ${\beta}3$ did not affect the expression of HDAC6 or MDR1. The down-regulation of tubulin ${\beta}3$ conferred sensitivity to anti-cancer drugs. Our results showed that tubulin ${\beta}3$ serves as a downstream target of HDAC3 and mediates resistance to microtubule-targeting drugs. Thus, the HDAC3-HDAC6-Tubulin ${\beta}$ axis can be employed for the development of anti-cancer drugs.

• 조명전기설비학회논문지
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• 제27권7호
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• pp.101-107
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• 2013

IEC Standards on lightning protection system specify the use of natural components as down conductors. This paper provides an analysis of problems revealed from our field investigation and survey conducted for the relevant experts in the construction site where natural components are used as down conductors. It also considers a suitable condition for installing natural components as down conductors in accordance with the latest version of the standard. As a result, when rebars of reinforced concrete are used as down conductors, vertical bars consisting of rebars of which thickness is not less than D13($127mm^2$) should be connected by welding, clamps or bound joints, using appropriate connection components conforming to IEC Standards. The lashed joints, however, shall not be applied for down conductors.

• 한국동물학회지
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• 제34권2호
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• pp.131-141
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• 1991

TPA나 PDGF를 처리로 인한 Protein Kinase C의 신호전달은 힌산화에 의해 일어난다. 그렇지만, PKC에 의해 인산화 되어지는 targeting protein은 TAP나 PDGF 처리시에는 분자량이 서로 다른 단백질들이 인산화가 되어졌다. TPA처리한 myoblast에서 분자량 20,000의 단백질이 인산화되었다. PDGF처리한 세포에서는 분자량 40,000의 단백질이 인산화된 반면에 TPA처리로 인산화 되었던 분자량 20,000의 단백질은 탈인산화 되었다. 이러한 결과들은 TPA와 PDGF가 신호전달계의 활성에 있어서 다를 뿐만 아니라 그들은 장시간의 처리동안 PKC의 down regulation에 관계되어 짐을 암시한다. 그러나 PDGF는 TPA의 경우에서 보다 빠른 down regulation을 유도하였다. 면역세포 화학적인 연구에서 PKC의 동위효소인 PKC II는 세포질에, PKC III는 세포질과 인에 각각 분포하고 있었다. Myoblast에 있어서 PCK두가지 형태의 동위효소의 발현은 이들 동위효소들이 signal transduction이나 down regulation의 각기 다른 경로에 개입되어 진다는 것을 암시한다.

• 대한의생명과학회지
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• 제19권4호
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• pp.348-352
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• 2013

microRNAs (miRNAs) play pivotal roles in controlling cell proliferation and differentiation. miRNA expression in human is becoming recognized as a new molecular mechanism of carcinogenesis. microRNA-34a (miR-34a), a member of the p53 network, was found to be regulated in multiple types of tumor. The purpose of this study was to define roles of miR-34a expression in cervical intraepithelial neoplasia with human papillomavirus infection, and its relationship with p53 protein expression. This study was performed to analyze expression of miR-34a by using qRT-PCR, and to evaluate p53 protein expression by using immunohistochemistry in 40 cases. Down-regulation of miR-34a expression was detected in 27 (67.5%) out of 40 cases and Immunoreactivity for p53 was found in 17 (42.5%) out of 40 cases. Nineteen (82.6%) of the 23 cases with a negative p53 expression showed a down-regulation miR-34a expression, there was a significant associations between miR-34a and p53 protein expression (P=0.04). These results suggest that miRNA-34a expression tend to be reduced depending on the advanced histologic grade, and down-regulation of miR-34a expression might be associated with inactivation of p53 protein expression by human papillomavirus infection.

• Archives of Pharmacal Research
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• 제18권5호
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• pp.301-307
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• 1995

In the particulate fraction obtained from PKC-down regulated K562 cells by treatment for 24 h with 200nM TPA, phosphorylation of two proteins with molecular weight, 100 kDa and 23 kDa (designated p100 and p23, respectvely) was depleted and addition of exogenous purified PKC to this fraction failed to testore their phosphorylation. However, in the soluble fraction, all of phosphoproteins abolished by long-term treatment with TPA were restored by exogenously added PKC. Phosphorylation of two proteins was increased by short-term tretment (20 min), and diminished with the persistant exposure to TPA as well as at a concentration as low as 1nM. When K562 cells were treated with 1 nM and 200 nM TPA for 24 h, phosphorylation of p100 was restored with or without exogenous PKC on 2-3day and 6day after removal of treated TPA, respectively. Two-dimensional electrophoresis of phosphoproteins revealed that phosphorylated p100 (pl=5.9) and p66 species were completely absent from the particulate fraction of K562 cells treated with 200nM TPA for 24 h. These results suggest that the interaction of sensitive endogenous substrates, p100 and p23 with the plasma membrane might be regulated by PKC-down regulation without displacement to the cytosol and the interaction of p100 with the membrane might be reveersible.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6245-6248
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• 2013

Aims: To study effects of down-regulation of pituitary tumor-transforming gene (PTTG) on proliferation and metastasis ability of the SCL-1 cutaneous squamous cell carcinoma (CSCC) cell line and explore related mechanisms. Methods: SCL-1 cells were divided into 3 groups (untreated, siRNA control and PTTG siRNA). Cell proliferation assays were performed using a CCK-8 kit and proliferation and metastasis ability were analyzed using Boyden chambers. In addition, expression of MMP-2 and MMP-9 was detected by r-time qPCR and Western blotting. Results: Down-regulation of PTTG could markedly inhibit cell proliferation in SCL-1 cells, compared to untreated and control siRNA groups (P < 0.05). Real-time qPCR demonstrated that expression levels of PTTG, MMP-2 and MMP-9 in the PTTG siRNA group were 0.8%, 23.2% and 21.3% of untreated levels. Western blotting revealed that expression of PTTG, MMP-2 and MMP-9 proteins in the PTTG siRNA group was obviously down-regulated. The numbers of migrating cells ($51.38{\pm}4.71$) in the PTTG siRNA group was obviously lower than that in untreated group ($131.33{\pm}6.12$) and the control siRNA group ($127.72{\pm}5.20$) (P < 0.05), suggesting that decrease of proliferation and metastasis ability mediated by PTTG knock-down may be closely correlated with down-regulation of MMP-2 and MMP-9 expression. Conclusion: Inhibition of PTTG expression may be a new target for therapy of CSCC.

• International Journal of Oral Biology
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• 제32권1호
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• pp.1-5
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• 2007

Receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) induces osteoclast formation from hematopoietic cells via up-regulation of positive regulators, including $NF-{\kappa}B$, c-Fos, microphthalmia transcription factor (Mitf), PU.1, and nuclear factor of activated T cells (NFAT) c1. In addition to the positive regulation by these transcription factors, RANKL appears to regulate negative regulators such as MafB and inhibitors of differentiation (Ids). Ids and MafB are abundantly expressed in osteoclast precursors, bone marrowderived monocyte/macrophage lineage cells (BMMs). Expression levels of these genes are significantly reduced by RANKL during osteoclastogenesis. Overexpression of these genes in BMMs inhibits the formation of tartarate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts by down-regulation of NFATc1 and osteoclast-associated receptor (OSCAR), which are important for osteoclast differentiation. Furthermore, reduced expression of these genes enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, RANKL induces osteoclastogenesis via up-regulation of positive regulators as well as down-regulation of negative regulators.