• Journal of Photoscience
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• v.9 no.2
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• pp.59-62
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• 2002

In chilling-sensitive plants, the donor side of Photosystem II is inhibited by the chilling treatment in the dark, while the acceptor side of Photosystem I is inhibited by the chilling under the moderate light. Since the addition of inhibitors of electron transfer from Photosystem II protects Photosystem I from chilling induced photoinhibition of Photosystem I, inhibition or down-regulation of Photosystem II activity in vivo may also protect Photosystem I from photoinhibition. It was revealed that dark-chilling pretreatment actually protected Photosystem I from photoinhibition. The results imply that down-regulation of Photosystem II under stress conditions may have a role to protect Photosystem I from photoinhibition.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.223-228
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• 2006

Several plant-derived cannabinoids and endogenous ligands for cannabinoid receptors such as 2-arachidonyl-glycerol have been known to inhibit interleukin-2 (IL-2) expression. In the present study, we utilized arachidonylethanolamide (AEA), a putative endogenous ligand for cannabinoid receptors, to determine whether AEA modulated the expression of IL-2. AEA inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced IL-2 protein secretion and mRNA expression in EL-4 mouse T-cells as determined by ELISA and RT-PCR, respectively. To further characterize the inhibitory mechanism of AEA at the transcriptional level, we performed promoter study for IL-2 gene in PMA/Io-stimulated EL-4 cells. AEA decreased the transcriptional activity of the nuclear factor of activated T-cells (NF-AT) as well as the IL-2 promoter activity. These results suggest that AEA suppresses IL-2 expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT.

• Journal of Ginseng Research
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• v.22 no.3
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• pp.216-221
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• 1998

We examined the anti-invasive activity of ginsenosides Rhl, Rha on the highly metastatic HT1080 human fibrosarcoma cell line. In vitro invasion assay showed ginsenoside Rhr reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber more than ginsenoside Rh1. Significant down-regulation of matrix metalloproteinase-9 (MMP-9) by ginsenosides Rh, and Rh2 was detected by Northern blot analysis. However, the expression of MMP-2 was not affected by Rh, and Rhr. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by Rhl after 0.5, 1 or 3 day-treatment but reduced after 6 day-treatment. However, the expression of TIMP-2 was not changed by treatment with Rh2. Plasminogen activator inhibitor (PAI) and urokinase-type plasmlnogen activator (uPA) were not changed by treatment with Rh1 and Rh2 for 3 and 6 days. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but MMP-2 after treatments with ginsenosides Rhl and Rha. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of ginsenosides Rhl and Rhr in the HT1080 cells.

• Nutritional Sciences
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• v.8 no.1
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• pp.16-22
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• 2005

The present study examined the effects of cyclooxygenase-2 (COX-2) inhibitor celecoxib or soy-isoflavones in the presence of estrogen on apoptosis related gene expression, COX-2 and mapkinase in 48-week old female rats. Expressions of bel-2 and bax proteins, which are known to be involved in the regulation of apoptosis, were investigated in mammary glands and heart tissues. The elevated expression of bel-2 expression was observed in mammary glands of celecoxib supplemented rats as well as soy-isoflavones. The mammary glands bel-2/bax ratio was found to be higher in celecoxib or soy-isoflavones supplemented rats. However, in heart tissues, expression of bel-2 and bax was in the order of control, celecoxib and soy-isoflavones. The up-regulation of COX-2 was observed in celecoxib or soy-isoflavones in mammary glands. 'The similar trend was not displayed with the mapkinase expression. In heart tissues, the down-regulation of COX-2 as well as mapkinase was observed in celecoxib or soy-isoflavones supplemented rats. Soy-isoflavones and celecoxib both had a similar regulatory pattern of bel-2, bax and COX-2 in mammary glands, and in heart tissues, only COX-2 exhibited a similar down-regulatory properly. These findings revealed that in estrogen sufficient state, celecoxib and soy-isoflavones might not exhibit proapoptotic potential or COX-2 inhibition in normal mammary glands.

• BMB Reports
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• v.31 no.4
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• pp.333-338
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• 1998

The sphingomyelin cycle and ceramide generation have been recognized as potential growth suppression signals in mammalian cells. Ceramide has been shown to induce differentiation, cell growth arrest, senescence, and apoptosis. Although the intracelluar target for the action of ceramide remains unknown, recent studies have demonstrated the role of cytosolic ceramideactivated protein phosphatase(CAPP). In this study, the cytotoxic effect of C2-ceramide, a synthetic cellpermeable ceramide analog, on HEp-2 cells and the mechanism by which ceramide induces cell death were investigated. The addition of exogenous C2-ceramide resulted in a concentration dependent cell death. Okadaic acid, a potent inhibitor of CAPP, enhanced ceramide-mediated cell death, which suggests that CAPP is not involved in this process. To understand the mechanism of action of ceramide, we studied the relationship between ceramide and c-Myc and pRb which are defined components of cell growth regulation. Western blot analyses revealed that C2-ceramide (10${\mu}M$) induced c-Myc down-regulation, but there were no significant changes in pRb. However, treatment of okadaic acid (10 nM) enhanced c-Myc and pRb down-regulation. Reduction of the amount of c-Myc and pRb occurred during HEp-2 cell death. These results suggest that the cytotoxic effect of ceramide in HEp-2 cells may not be mediated through the action of CAPP and that the downstream target for ceramide is c-Myc and pRb.

• Animal cells and systems
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• v.8 no.1
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• pp.49-55
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• 2004

In vertebrates, multisubunit cofactors regulate gene expression through interacting with cell-type- and gene-specific DNA-binding proteins in a chromatin-selective manner. ADD1/SREBP1c regulates fatty acid metabolism and insulin-dependent gene expression through binding to SRE and E-box motif with dual DNA binding specificity. Although its transcriptional and post-translational regulation has been extensively studied, its regulation by interacting proteins is not well understood. To identify cellular proteins that associate with nuclear form of ADD1/SEBP1c, we employed the GST pull-down system with Hela cell nuclei extract. In this study, we demonstrated that Ku proteins interact specifically with ADD1/SREP1c protein. GST pull-down combined with peptide sequencing analysis revealed that Ku80 binds to ADD1/SREBP1c in vitro. Additionally, western blot analysis showed that Ku70, a heterodimerizing partner of Ku80, also associates with ADD1/SREBP1c. Furthermore, co-transfection of Ku70/Ku80 with ADD1/SREBP1c enhanced the transcriptional activity of ADD1/SREBP1c. Taken together, these results suggest that the Ku proteins might be involved in the lipogenic and/or adipogenic gene expression through interacting with ADD1/SREBP1c.

• BMB Reports
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• v.44 no.1
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• pp.28-33
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• 2011

MicroRNAs are potential key regulators in mesenchymal stem cells chondrogenic differentiation. However, there were few reports about the accurate effects of miRNAs on chondrogenic differentiation. To investigate the mechanisms of miRNAs-mediated regulation during the process, we performed miRNAs microarray in MSCs at four different stages of TGF-${\beta}3$-induced chondrogenic differentiation. We observed that eight miRNAs were significantly up-regulated and five miRNAs were downregulated. Interestingly, we found two miRNAs clusters, miR-143/145 and miR-132/212, kept on down-regulation in the process. Using bioinformatics approaches, we analyzed the target genes of these differentially expressed miRNAs and found a series of them correlated with the process of chondrogenesis. Furthermore, the qPCR results showed that the up-regulated (or down-regulated) expression of miRNAs were inversely associated with the expression of predicted target genes. Our results first revealed the expression profiles of miRNAs in chondrogenic differentiation of MSCs and provided a new insight on complicated regulation mechanisms of chondrogenesis.

• Archives of Pharmacal Research
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• v.25 no.1
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• pp.93-101
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• 2002

The extract of European mistletoe ( Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coleratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisns for these effects. We showed that VCA induced atoptosis in both SK-Hep-1 and Hep 3B (p53-negative) cells through p53- and p21 -independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondria controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.

• Parasites, Hosts and Diseases
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• v.52 no.2
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• pp.131-135
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• 2014

Acanthamoeba cysts are resistant to unfavorable physiological conditions and various disinfectants. Acanthamoeba cysts have 2 walls containing various sugar moieties, and in particular, one third of the inner wall is composed of cellulose. In this study, it has been shown that down-regulation of cellulose synthase by small interfering RNA (siRNA) significantly inhibits the formation of mature Acanthamoeba castellanii cysts. Calcofluor white staining and transmission electron microscopy revealed that siRNA transfected amoeba failed to form an inner wall during encystation and thus are likely to be more vulnerable. In addition, the expression of xylose isomerase, which is involved in cyst wall formation, was not altered in cellulose synthase down-regulated amoeba, indicating that cellulose synthase is a crucial factor for inner wall formation by Acanthamoeba during encystation.

• BMB Reports
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• v.50 no.11
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• pp.560-565
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• 2017

Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta ($GSK-3{\beta}$). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity.