• Molecules and Cells
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• v.28 no.5
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• pp.431-439
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• 2009

Rice Oryza sativa accelerated cell death and resistance 1 (OsACDR1) encodes a putative Raf-like mitogen-activated protein kinase kinase kinase (MAPKKK). We had previously reported upregulation of the OsACDR1 transcript by a range of environmental stimuli involved in eliciting defense-related pathways. Here we apply biochemical, gain and loss-of-function approaches to characterize OsACDR1 function in rice. The OsACDR1 protein showed autophosphorylation and possessed kinase activity. Rice plants overexpressing OsACDR1 exhibited spontaneous hypersensitive response (HR)-like lesions on leaves, upregulation of defense-related marker genes and accumulation of phenolic compounds and secondary metabolites (phytoalexins). These transgenic plants also acquired enhanced resistance to a fungal pathogen (Magnaporthe grisea) and showed inhibition of appressorial penetration on the leaf surface. In contrast, loss-of-function and RNA silenced OsACDR1 rice mutant plants showed downregulation of defense-related marker genes expressions and susceptibility to M. grisea. Furthermore, transient expression of an OsACDR1:GFP fusion protein in rice protoplast and onion epidermal cells revealed its localization to the nucleus. These results indicate that OsACDR1 plays an important role in the positive regulation of disease resistance in rice.

• Journal of Life Science
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• v.32 no.6
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• pp.421-429
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• 2022

The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

• Fisheries and Aquatic Sciences
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• v.4 no.4
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• pp.180-185
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• 2001

Al and Cd-induced inhibition of vitellogenin (VTG) production was examined at the estrogen receptor (ER) level in rainbow trout Oncorhynchus mykiss hepatocytes. The binding of $[^3H]$ $estradiol-17\beta\;(E_2)$ to hepatocytes reached a plateau 3 days after addition of $E_2\;(2\times\;10^{-6} M)$to the medium. The binding activity was linearly reduced with the increased concentrations $(-10^{-5}\;M)$ of 4-hydroxy-tamoxifen (4-OHT) and specific binding linearly increased with the increased doses of $[^3H]\;E_2$, indicating that the radioligand bound to ER. Al $(-10^{-4}\;M)$and Cd $(10^{-6}\;M)$ as well as 4-OHT $(10^{-6}\;M)$ significantly reduced the $[^3H]\;E_2$-binding activity by $30­40\%$, while they completely inhibited VTG production. Al and Cd had no effect on $E_2-human$ $ER\alpha$ binding activity at any concentrations used $(-10^5\;nM\;each)$. These results suggested that Al and Cd inhibited VTG production in part by interfereing with the ER level. Inhibitory effects of these metals on the $E_z-dependent$ upregulation of ER activity are also discussed.

• Journal of Photoscience
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• v.9 no.2
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• pp.201-204
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• 2002

Epidermal cells produce a panel of antioxidants as well as cytokines after UVB irradiation, which counteract reactive oxygen species, however, how these antioxidants might regulate melanogenesis is unclear. An important constituent of the cellular antioxidant buffering system which controls the redox state of proteins is thioredoxin (TRX), a 13-kD protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biological functions similar to cytokines. TRX suppressed the UVB-induced production and secretion of $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocyte (KC)s. Further, L-cysteine, N-acetyl-cysteine, $\alpha$-tocopheryl ferulate showed suppressive effect on UVB-induced POMC mRNA expression. However, TRX released from UVB-irradiated KCs stimulated melanogenesis by up-regulating MSH receptor expression and its binding activity in melanocyte (MC)s. UVB-induced KC derived cytokines such as IL1, IL6, and ET1 upregulated MSH-receptor binding ability as well as MCl-R mRNA expression in cultured normal human MCs. MCl-R has a tendency to be upregulated by UVB-induced KC-derived cytokines as well as by direct UVB irradiation. These results suggest that antioxidants such as TRX suppresses UVB induction of POMC, but in the case of MCl-R, this gene can be mainly in the trend of upregulation by UVB-induced KC-derived factors including TRX.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.225-232
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• 2015

We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.

• BMB Reports
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• v.42 no.2
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• pp.86-90
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• 2009

Deletion of smpd3 induces osteogenesis and dentinogenesis imperfecta in mice. smpd3 is highly elevated in the parietal bones of developing mouse calvaria, but not in sutural mesenchymes. Here, we examine the mechanism of smpd3 regulation, which involves BMP2 stimulation of Runx2. smpd3 mRNA expression increased in response to BMP2 treatment and Runx2 transfection in C2C12 cells. The Runx2-responsive element (RRE) encoded within the -562 to -557 region is important for activation of the smpd3 promoter by Runx2. Electrophoretic mobility shift assays revealed that Runx2 binds strongly to the -355 to -350 RRE and less strongly to the -562 to -557 site. Thus, the smpd3 promoter is activated by BMP2 and is directly regulated by the Runx2 transcription factor. This novel description of smpd3 regulation will aid further studies of bone development and osteogenesis.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.171-177
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• 2010

Appetite is inhibited by the anorexigenic neuropeptides POMC (proopiomelanocortin) and CART (cocaine-amphetamine-regulated transcript) in the hypothalamus. The present study was performed to examine the inhibitory effects of baicalin against food intake and the upregulation of POMC/CART. Short-term food intake (48 h) was significantly inhibited by treatment with baicalin (10 mg/kg, p<0.05) in C57BL/6 mice. Immunohistochemical analysis showed that baicalin upregulated POMC and CART levels in the arcuate nucleus of the hypothalamus. These effects were also examined using an in vitro system. pPOMC-Luc or pCART-Luc plasmids were transformed into mouse N29-2 neuronal and human SH-SY5Y cells, and the activities of baicalin were examined in these cells. Baicalin increased POMC and CART promoter-driven luciferase activity in a dose-dependent manner without cytotoxic effects. These results suggest that baicalin downregulates short-term food intake while upregulating POMC and CART expression.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.693-699
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• 2012

This study was conducted to investigate the effects of Woohwangcheungsimweun (ox bezoar), deer antlers, and wild ginseng on induction of cardiomyocyte differentiation using the established mouse embryonic stem (ES) cells. The expression of atrial natriuretic peptide (ANP) was highest in Woohwangcheungsimweun treatment group. The expression of rabbit anti-GATA-4(GATA-4) and troponin (TnI) were highest in wild ginseng and Woohwangcheungsimweun treatment groups, respectively. Fluorescence activated cell sorting (FACS) analysis showed that the expression of ANP was highest in Dimethyl sulfoxide(DMSO) and Woohwangcheungsimweun treatment groups. The expression of GATA-4 was relatively high in wild ginseng treatment group. The expression of TnI was highest in Woohwangcheungsimweun treatment group. In the gene expression analysis, DMSO greatly inhibited GATA-4 expression to 25% of control. Woohwangcheungsimweun treatment caused to increase cTnI and cardiac ANP expression significantly. Wild ginseng extract upregulated GATA-4 gene expression. In conclusion, DMSO widely used as cardiomyocyte differentiation inducer did not show significant effects on the expression of ANP, GATA-4 and TnI in this study. Woohwangcheungsimweun showed upregulation of ANP and TnI expression. Wild ginseng extract showed greater effects than DMSO on GATA-4 expression. These results might suggest that the combination of Woohwangcheungsimweun and wild ginseng extract treatment can be expected to increase expressions of all three genes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2207-2212
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• 2013

Cancer prevention is rapidly emerging as a major strategy to reduce cancer mortality. In the field of breast cancer, significant strides have recently been made in the understanding of underlying preventive mechanisms. Currently, three major strategies have been linked to an increase in breast cancer risk: obesity, lack of physical exercise, and high levels of saturated dietary fat. As a result, prevention strategies for breast cancer are usually centered on these lifestyle factors. Unfortunately, there remains controversy regarding epidemiological studies that seek to determine the benefit of these lifestyle changes. We have identified crucial mechanisms that may help clarify these conflicting studies. For example, recent reports with olive oil have demonstrated that it may influence crucial transcription factors and reduce breast tumor aggressiveness by targeting HER2. Similarly, physical exercise reduces sex hormone levels, which may help protect against breast cancer. Obesity promotes tumor cell growth and cell survival through upregulation of leptin and insulin-like growth factors. This review seeks to discuss these underlying mechanisms, and more behind the three major prevention strategies, as a means of understanding how breast cancer can be prevented.

• Korean Journal of Pharmacognosy
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• v.44 no.4
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• pp.397-401
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• 2013

The Galkun-Whanglyeon-Whanggum-Tang, an officially standardized mixture of traditional herbal medicines used in Korea and China, consists of Pueraria lobata, Scullellaria baicalensis, Coptis chinensis and Glycyrrhiza uralensis at a ratio of 6:9:3:2.4. In this study, we evaluated the effect of lowering lipid accumulation in blood by treatment of Galkun-Whanglyeon-Whanggum-Tang in Apo E(-/-) atherosclerotic animal model. ApoE/mice fed with 1.25% cholesterol, 7.5% cocoa butter and 0.5% sodium cholate diet were orally given vehicle or Galkun-Whanglyeon-Whanggum-Tang(10, 100 and 300 mg/kg/day) for 12 weeks. Serum levels of triglyceride(TG), total cholestrerol(TC), low-density lipoprotein(LDL) and high-density lipoprotein(HDL) were analyzed, and PPAR-${\alpha}$ and PPAR-${\gamma}$ were examined by Western blotting analysis. Galkun-Whanglyeon- Whanggum-Tang decreased serum levels of TG, TC and LDL, but not HDL in ApoE/mice. In parallel, Galkun-Whanglyeon-Whanggum-Tang treatment showed the increased activity of PPAR-${\alpha}$ and PPAR-${\gamma}$ in hepatocytes. In summary, Galkun-Whanglyeon-Whanggum-Tang can reduce lipid accumulation in blood, and this effect might be accompanied by the upregulation of PPAR-${\alpha}$ and PPAR-${\gamma}$ in Apo E(-/-) atherosclerotic mouse model.