• Preventive Nutrition and Food Science
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• v.9 no.3
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• pp.270-275
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• 2004

Previous studies have shown that kimchi and kimchi-derived 3-(4'-hydroxyl-3', 5'-dimethoxyphenyl) propionic acid have anti-oxidative and hypolipidemic effects in rats and rabbits. This study was designed to investigate whether chemically synthesized 3-(4'-hydroxyl-3', 5' -dimethoxyphenyl) propionic acid (HDMPPA) may ameliorate oxidative stress through the regulation of nuclear factor KB (NFkB) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Treatment of RAW 264.7 cells with 400 uM of HDMPPA significantly reduced LPS-stimulated nitric oxide (NO) production. Treatments with HDMPPA at 100 uM to 400 uM concentrations significantly elevated glutathione (GSH) level. However, cell viability and thiobarbituric acid-reactive substances (TBARS) concentrations were not affected by the concentrations of HDMPPA used. The specific DNA binding activities of NFKB, a transcription factor which is sensitive to oxidative stress, were not down-regulated by HDMPPA treatments. These results suggest that HDMPPA may have weak anti-oxidative activity against LPS challenge by scavenging NO and stimulating GSH production.

• The Journal of Korean Medicine
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• v.22 no.3
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• pp.92-97
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• 2001

목적 :본 연구는 최근 임상에서 많이 사용하는 자하거 약침액이 과산화수소($H_2O_2$)로 야기된 송과선 세포의 Apoptosis에 있어서 세포 보호에 미치는 영향과 그 기전을 분석하였다. 방법 :송과선 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전을 관찰하기 위하여 면역세포화학법. 세포화학법 및 reverse transcription-polymerase chain reaction (RT-PCR)을 시행하였다. 결과 : 자하거 약침액 투여군에서는 nuclear factor kappa B (NFkB), inducible nitric oxide synthase (iNOS), nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase의 발현이 $H_2O_2$ 투여군보다 감소하였다. RT-PCR에서는 caspase-3의 발현이 자하거 약침액 투여군에서 $H_2O_2$ 투여군보다 억제되었다. 결론： 이상의 결과를 통하여 자하거 약침액이 $H_2O_2$로 유발된 Apoptosis에서 세포보호 효과가 있으며 그 기전은 iNOS와 caspase-3의 억제에 기인할 가능성을 시사한다고 하겠다.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.503-511
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• 2018

Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NF-kB, ROCK and PKC pathways. In the case of PKC activation, it was observed that $PKC{\delta}$ and $PKC{\mu}$ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve $PKC{\delta}$ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.

• International Journal of Oral Biology
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• v.33 no.2
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• pp.51-58
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• 2008

A mutation of UNCL, an inner nuclear membrane RNAbinding protein, has been found to eliminate mechanotransduction in Drosophila. UNCL is expressed in human periodontal tissue including in periodontal ligament (PDL) fibroblasts. However, it is unclear how a mechanical stimulus is translated into cellular responses in PDL fibroblasts. The aim of this study was to evaluate the effect of UNCl on mechanical stress related genes in PDL fibroblasts in response to mechanical stress. The mRNA of TGF-$\beta$, COX-2, and MMP-2 was up-regulated after UNCL inactivation in PDL fibroblasts under the compression force. Under the tensile force, inactivation of UNCL decreased the expression of Biglycan, RANKL, MMP-2, and TIMP-2 mRNAs while it increased the expression of TIMP-1. p38-MAPK was expressed in PDL fibroblasts under compression forces whereas phospho-ERK1/2, p65-NFkB, and c-fos were expressed under tension forces. The expression and phosphorylation of the mechanical stress related genes, kinases, and transcription factors were changed according to the types of stress. Furthermore, most of them were regulated by the inactivation of UNCL. This suggests that UNCL is involved in the regulation of mechanical stress related genes through the signaling pathway in PDL fibroblasts.

• BMB Reports
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• v.45 no.5
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• pp.287-292
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• 2012

FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti-apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-${\alpha}$. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.53 no.1
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• pp.123-131
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• 2020

In this study, we investigated the protective effects of a Neutrase enzymatic hydrolysate derived from Korea pen shell Atrina pectinata (APN) against hydrogen peroxide (H₂O₂)-induced oxidative damage in hepatocytes. First, we confirmed that APN has antioxidant activities by scavenging 2,2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS⁺) and H₂O₂ and increasing oxygen radical absorbance capacity (ORAC) value. Also, the treatment of APN increased the cell viability by reducing the intracellular reactive oxygen species (ROS) production in H₂O₂-stimulated hepatocytes. In addition, APN decreased the sub-G₁ DNA contents and the apoptotic body formation increased by H₂O₂ stimulation. Moreover, APN modulated the protein expression of apoptosis related molecules (Bcl-2, Bax and p53) by suppressing the activation of nuclear factor NFkB and ERK/p38 signaling in H₂O₂-stimulated hepatocytes. Furthermore, APN led to the activation of Nrf2/HO-1signaling known as antioxidant systems. These results suggest APN protects hepatocytes against oxidative damages caused by H₂O₂ stimulation.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• Tuberculosis and Respiratory Diseases
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• v.52 no.6
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• pp.616-626
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• 2002

Background : The present study was performed to further improve our understanding of molecular mechanisms involved in the activation of NFkB, a major transcriptional factor involved in the inflammatory response in the lung, by particulate matter in lung epithelial cells with an aerodynamic diameter of less than $2.5{\mu}m$(PM2.5). Materials and Methods : Immediate production of reactive oxygen species (ROS) and nitrogen species (RNS), with the PM2.5 induced expression of inducible nitric oxide synthase (iNOS), $I{\kappa}B$ degradation and $NF{\kappa}B$-dependent transcriptional activity, in 549 cells, were monitored. Addition, we also examined the effect of the iNOS inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL), on the PM2.5-induced $NF{\kappa}B$ activation in A549 cells. Results : The rapid degradation of $I{\kappa}B$ and the increase of transcriptional activity of the $NF{\kappa}B$-dependent promotor were observed in A549 cells exposed to PM2.5. The immediate production of ROS in response to PM2.5 in A549 cells was not clearly detected, although immediate responses were observed in RAW264.7 cells. A 549 cells, cultured in the presence of PM2.5, produced an increase in NO, which was noticeably significant after 15 min of exposure with the expression of iNOS mRNA. The addition of L-NIL, an iNOS inhibitor, significantly inhibited the PM2.5-induced $I{\kappa}B$ degradation and the increase of the $NF{\kappa}B$-dependent transcriptional activity. Conclusion : These results suggest that PM2.5 stimulates the immediate production of RNS, leading to the activation of $NF{\kappa}B$ in the pulmonary epithelium.

• Journal of Korean Neurosurgical Society
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• v.59 no.6
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• pp.551-558
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• 2016

Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.669-673
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• 2011

To prevent and treat the osteoporotic fracture, more attention should be paid in old age patients. Osteoclast which has ability to bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Rubi Fructus has been widely used in Oriental medicine. Extracts of the leaves and fruit of Rubus species have been used in various countries as natural remedies to treat diabetes, infections, colic, and burns. However, the effect of extract of Rubi Fructus (fruit of Rubus coreanus Miq.) in osteoclast differentiation remains unknown. Thus, we evaluated the effect of Rubi Fructus on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation. Here we found that Rubi Fructus significantly inhibited osteoclast differentiation induced by RANKL. Rubi Fructus suppressed the activation of p38 pathway and NFkB in bone marrow macrophages (BMMs) treated with RANKL. Also, Rubi Fructus significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Rubi Fructus greatly inhibited the protein expression of c-fos and NFATc1. especially in the case of NFATc1 expression, a master transcription factor of the differentiation of osteoclasts is very important step for osteoclastogenesis. Taken together, our results demonstrated that Rubi Fructus may be useful treatment option of bone-related disease such as osteoporosis and rheumatoid arthritis.