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Effect of Epigallocatechin Gallate on Phosphoinositide 3-kinase/Akt and Glycogen Synthase Kinase-3 Pathway in Oxidative-stressed N18D3 Cells Following $H_2O_2$ Exposure (산화성 손상을 받은 N18D3세포에서 Epigallocatechin gallate가 Phosphoinositide 3-kinase/Akt 및 Glycogen synthase kinase-3경로에 미치는 효과)

  • Koh, Seong Ho;Kwon, Hyug Sung;Oh, Hwa Soon;Oh, Jae Ho;Park, Ynun Joo;Kim, Jun Gyou;Kim, Ki Sok;Kim, Yang Soon;Yang, Ki Hwa;Kim, Seung U.;Kim, Seung H.;Jung, Hai Kwu
    • Korean Journal of Clinical Pharmacy
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    • v.13 no.1
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    • pp.29-39
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    • 2003
  • Neurodegenerative disorders are associated with apoptosis as a causing factor or an inducer. On the other hand, it has been reported that epigallocatechin gallate (EUG), one of antioxidants and flavonoids, and z-VAD-fmk, a nonselective caspase inhibitor, suppress oxidative-radical-stress-induced apoptosis. However, it is not yet known what is the effects of EGCG and z-VAD-fmk on the apoptotic pathway is through phosphoinositide 3-kinase (PI3K), Akt and glycogen synthase kinase-3 (GSK-3) as well as mitochondria, caspase-3 and poly (ADP-ribose) polymerase (PARP). We investigated the effects of EGCG by using $H_2O_2$ treated N18D3 cells, mouse DRG hybrid neurons. Methods: Following 30 min $100\;{\mu}m\;H_2O_2$ exposure, the viability of N18D3 cells (not pretreated vs. EGCG or z-VAD-fmk pretreated) was evaluated by using MTT assay. The effect of EGCG on immunoreactivity (IR) of cytochrome c, caspase-3, PARP, PI3K/Akt and GSK-3 was examined by using Western blot, and was compared with that of z-Y4D-fmk. Results: EGCG or z-VAD-fmk pretreated N18D3 cells showed increased viability. Dose-dependent inhibition of caspase-3 activation accompanied by PARP cleavage were demonstrated by pretreatment of both agents. However, inhibition of cytochrome c release was only detected in EGCG pretreated N18D3 cells. On the pathway through PI3K/Akt and GSK-3, however, the result of Western blot in EGCG pretreated N18D3 cells showed decreased IR of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and GSK-3, and contrasted with that in z-VAD-fmk pretreated N18D3 cells showing no changes on each molecule. Conclusion: These data show that EGCG affects apoptotic pathway through upstream signal including PI3K/Akt and GSK-3 pathway as well as downstream signal including cytochrome c and caspase-3 pathway. Therefore, these results suggest that EGCG mediated activation of PI3K/Akt and inhibition GSK-B could be new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

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Antioxidant and Neuroprotective Effects of Green Tea Seed Shell Ethanol Extracts (녹차씨껍질 에탄올 추출물의 항산화 활성 및 신경세포 보호 효과)

  • Sung, Nak-Yun;Song, Hayeon;Ahn, Dong-Hyun;Yoo, Yung-Choon;Byun, Eui-Baek;Jang, Beom-Su;Park, Chulhwan;Park, Won-Jong;Byun, Eui-Hong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.958-965
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    • 2016
  • The objective of this study was to evaluate the antioxidant activity of green tea seed shell as an industrial byproduct. Green tea seed shell extract (GTSSE) was obtained by ethanol extraction, and the yield was $1.4{\pm}0.22%$. The radical scavenging activities [1,1-diphenyl-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], xanthine oxidase inhibition activity, and reducing power of GTSSE dose-dependently increased. To estimate the neuroprotective effect of GTSSE, viability was tested in HT22 mouse hippocampal cells. GTSSE treatment induced cytotoxicity at a concentration higher than $100{\mu}g/mL$ but not at a concentration lower than $50{\mu}g/mL$. Using this optimal concentration range, GTSSE treatment significantly increased cell viability in $H_2O_2$-treated HT22 cells. Further, GTSSE treatment increased superoxide dismutase activity and decreased the malonaldehyde level, a product of lipid peroxidation, in HT22 cells. Therefore, these results indicate that green tea seed shell extract may be useful for the development of antioxidant materials and have potential activity to prevent and treat neuro-degenerative diseases such as Alzheimer's disease.

Protective Effects of New Herbal Composition (MH-30) against Radiation Injuries in Hematopoietic and Self-Renewal Tissues (생약조성물(MH-30)의 면역조혈계 및 재생조직 방사선 손상에 대한 방호 효과)

  • Jung, Uhee;Park, Hae-Ran;Lee, Ho-Yong;Baek, Ga-Young;Jo, Sung-Kee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.948-957
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    • 2016
  • We previously developed an herbal composition (HemoHIM) based on the water extracts of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix to protect and recover hematopoietic and intestinal tissues against radiation injuries. In this study, to develop a composition with improved activities based on enhanced fat-soluble polyphenol contents, we prepared a new herbal composition, MH-30, from the above three herbs by 30% ethanol extraction and hot water extraction. HPLC analysis of the ethanol fractions of MH-30 and HemoHIM revealed that MH-30 had higher contents of many fat-soluble polyphenol compounds than HemoHIM (8.7-fold increase for decursin), whereas contents of water-soluble polyphenol compounds showed little differences between the two compositions. Then, we evaluated MH-30 and HemoHIM for their in vitro antioxidant and immune cell-stimulating activities as well as in vivo protective effects against radiation injuries in hematopoietic and self-renewal tissues. In antioxidant activity assays, MH-30 showed higher hydroxyl radical scavenging activity than HemoHIM (1.4- to 1.9-fold for compositions and 2.3- to 4.5-fold for ethanol fractions). On the other hand, MH-30 and HemoHIM exhibited similar immune cell-stimulating activities as measured by in vitro lymphocyte proliferation. MH-30 increased endogenous spleen colony formation, decreased bone marrow cell apoptosis, and enhanced survival of intestinal crypts in irradiated mice, demonstrating effective protection of MH-30 against radiation-induced injuries in hematopoietic and self-renewal tissues. The 30-day survival rate of lethally irradiated mice, a comprehensive index for radioprotective efficacy, was also elevated by MH-30. Noticeably, MH-30 showed higher protective effects than HemoHIM in all mouse experiments. These results demonstrate that MH-30 can protect hematopoietic and self-renewal tissues against radiation injuries more effectively than HemoHIM. Therefore, MH-30 can be a good candidate to reduce radiation injuries in hematopoietic and self-renewal tissues incurred by radiation accidents or cancer radiation therapy.

Measuring the Third-Person Effects of Public Opinion Polls: Focusing On Online Polls (여론조사보도에 대한 제3자효과 검증: 온라인 여론조사를 주목하며)

  • Kim, Sung-Tae;Willnat, Las;Weaver, David
    • Korean journal of communication and information
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    • v.32
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    • pp.49-73
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    • 2006
  • During the past decades, public opinion polls have become an ubiquitous tool for probing the complexity of people's beliefs and attitudes on a wide variety of issues. Especially since the late 1970s, the use of polls by news organizations has increased dramatically. Along with the proliferation of traditional polls, in the past few years pollsters and news organizations have come to recognize the advantages of online polls. Increasingly there has been more effort to take the pulse of the public through the Internet. With the Internet's rapid growth during the past years, advocates of online polling often emphasize the relative advantages over traditional polls. Researchers from Harris Black International Ltd., for example, argue that "Internet polling is less expensive and faster and offers higher response rates than telephone surveys." Moreover, since many of the newer online polls draw respondents from large databases of registered Internet users, results of online polls have become more balanced. A series of Harris Black online polls conducted during the 1998 gubernatorial and senatorial elections, for example, has accurately projected the winners in 21 of the 22 races it tracked. Many researchers, however, severely criticize online polls for not being representative of the larger population. Despite the often enormous number of participants, Internet users who participate in online polls tend to be younger, better educated and more affluent than the general population. As Traugott pointed out, the people polled in Internet surveys are a "self selected" group, and thus "have volunteered to be part of the test sample, which could mean they are more comfortable with technology, more informed about news and events ... than Americans who aren't online." The fact that users of online polls are self selected and demographically very different from Americans who have no access to the Internet is likely to influence the estimates of what the majority of people think about social or political issues. One of the goals of this study is therefore to analyze whether people perceive traditional and online public opinion polls differently. While most people might not differentiate sufficiently between traditional random sample polls and non representative online polls, some audiences might perceive online polls as more useful and representative. Since most online polls allow some form of direct participation, mostly in the form of an instant vote by mouse click, and often present their findings based on huge numbers of respondents, consumers of these polls might perceive them as more accurate, representative or reliable than traditional random sample polls. If that is true, perceptions of public opinion in society could be significantly distorted for those who rely on or participate in online polls. In addition to investigating how people perceive random sample and online polls, this study focuses on the perceived impact of public opinion polls. Similar to these past studies, which focused on how public opinion polls can influence the perception of mass opinion, this study will analyze how people perceive the effects of polls on themselves and other people. This interest springs from prior studies of the "third person effect," which have found that people often tend to perceive that persuasive communications exert a stronger influence on others than on themselves. While most studies concerned with the political effects of public opinion polls show that exit polls and early reporting of election returns have only weak or no effects on the outcome of election campaigns, some empirical findings suggest that exposure to polls can move people's opinions both toward and away from perceived majority opinion. Thus, if people indeed believe that polls influence others more than themselves, perceptions of majority opinion could be significantly altered because people might anticipate that others will react more strongly to poll results.

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The Quality Characteristics of American Sauce Prepared with Different Amounts of Salt (소금 첨가량에 따른 아메리칸소스의 품질 특성)

  • Kim, Dong-Seok;Lee, Se-Hee;Seoung, Tae-Jong
    • Culinary science and hospitality research
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    • v.18 no.3
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    • pp.163-179
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    • 2012
  • This study was prepared to develop American sauce with different amounts of salt through high pressure extraction and examined difference in its mechanical and sensory characteristics. Furthermore, it aimed to provide practical materials for the mass production of American sauce and other crustacean sauce products and to contribute to the development of products with superior quality and functionality by standardizing traditional cooking techniques in the food service industry. In American sauce, salt content did not have a significant effect on water content and ash content but had a significant effect on color, pH and salinity. Na and K contents increased with increasing salt content. In addition, Mg and P contents were highest in J4 containing 0.4% of salt, but they did not show any regular tendency according to salt content. For total free amino acids, 29 kinds were detected in J0 and J1, 30 in J2, 31 in J3, and 33 in J4. Detection was highest in J3 containing 0.3% of salt, and the content level was highest particularly for arginine among essential amino acids, for glutamic acid, alanine, serine, ${\beta}$-alanine and ${\alpha}$-aminoadipic acid among flavor enhancing amino acids, and for ${\gamma}$-Aminoisobutyric acid among other amino acids. We measured lipid peroxidation in American sauce using lipid extracted from a mouse brain and confirmed that the amount of antioxidant substances extracted was largest in J0 containing no salt. The results of measuring lipid peroxidation and DPPH showed that the antioxidant effect was high when salt was not contained. In the results of the sensory test, overall quality was highest in J3 containing 0.3% of salt, showing that the addition of salt affects the evaluation of overall quality. Summing up the presents of this study as presented above, we cannot expect an effect of antioxidant functionality; however, according to the results of the mechanical quality evaluation and the sensory test, American sauce containing 0.3% of salt is considered the optimal product in terms of quality. Using these results as practical materials for the mass production of crustacean sauce products, we expect to standardize traditional cooking techniques in the food service industry and to develop products with high quality and functionality.

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An Experimental Study on Radioprotective Effect of DDC, MEA, and WR-2721 (DDC, MEA, WR-2721의 방사선(放射線) 방호효과(防護效果)에 관(關)한 연구(硏究))

  • Chung, In-Young;Koh, Joo-Hwan;Chung, Hyun-Woo;Chil, Soo-Yil;Yoo, Seong-Yul;Koh, Kyoung-Hwan
    • Journal of Radiation Protection and Research
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    • v.11 no.2
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    • pp.114-122
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    • 1986
  • At present, the treatments of the radiation-induced diseases are only performing by the palliative treatment technique. Moreover, radiation protective agents are a little toxic for human being and this seriously limits their applicability with various complications in clinical uses. Accordingly, as a part of the aim of gain of the basic data for protective roles of some radioprotectors, the present investigation was carried out to evaluate the comparative radioprotective effects by the administration of DDC, MEA, WR-2721. Results are shown for statistically significant analysis and correlation with each group as follows; 1. The proper doses of the radioprotectors were DDC; 1,550 mg/kg, MEA; 450 mg/kg, WR-2721; 780 mg/kg of the mouse body weight. 2. DMF(Dose modification factor) of LD 50/10 and LD 50/30 for whole body irradiation was DDC; 1.2, MEA; 1.4, WR-2721; 1.9 and DDC; 1.7, MEA; 1.8, WR-2721; 2.5 respectively. 3. DMF for radiation reaction of jejunal crypt was DDC: 1.07, MEA: 1.21 and WR-2721: 1.76 and that of jejunal crypt cell was DDC: 1.04, MEA: 1.08 and WR-2721: 1.38 respectively. 4. Conclusively, WR-2721 was the most effective drung among the three radioprotectors and this result must be a supportive data for further study for clinical application.

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Anti-oxidative and Anti-inflammatory Effects of Genistein in BALB/c Mice Injected with LPS (LPS 주사한 BALB/c 마우스에서 Genistein의 산화적 스트레스 억제효과 및 항염증 효과)

  • Cho, Hye-Yeon;Noh, Kyung-Hee;Cho, Mi-Kyung;Jang, Ji-Hyun;Lee, Mi-Ok;Kim, So-Hee;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.9
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    • pp.1126-1135
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    • 2008
  • This study was carried out to investigate the anti-oxidative and anti-inflammatory actions of genistein in BALB/c mice injected with lopopolysaccharide (LPS), called endotoxin. Mice (10 weeks of age) weighing approximately 20 g were divided into 4 groups. Endotoxin shock was induced by intraperitoneal injection of LPS (100 mg/kg BW). LPS and genistein+LPS groups were injected with LPS 30 min after phosphate buffered saline (PBS) solution and genistein (200 mg/kg BW) injections, respectively. Genistein group was injected with genistein, followed by PBS, while PBS group received two injections of PBS. Superoxide anion generation of peritoneal macrophage cells was significantly (p<0.05) lower in the genistein+LPS group than in the LPS injection group at 8 h after intraperitoneal injection, while SOD activity was significantly higher in genistien+LPS group than LPS group. Tumor necrosis factor-$\alpha$ levels of plasma were significant lower (p<0.05) in the genistein+LPS injection group than LPS group at 8 h after intraperitoneal injection. Plasma TBARS was lower in genistein+LPS group than LPS group, while hepatic TBARS were not different among groups. Hepatic glutathione concentrations and antioxidant enzyme activities were ignificantly higher in the genistein+LPS group than in the LPS group at 1 h and 8 h after intraperitoneal injection. Nuclear factor-kappa B (NF-${\kappa}B$) transactivation was significantly (p<0.05) inhibited in LPS group. These results demonstrate genistein may ameliorate inflammatory diseases through inhibition of NF-${\kappa}B$ transactivation and oxidative stress, which may be mediated partially by anti-oxidative effect of genistein.

Effects Unripe and Ripe Rubus coreanus Miquel on Peritoneal Macrophage Gene Expression Using cDNA Microarray Analysis (미숙과와 성숙과 복분자의 섭취가 복강 Macrophages의 유전자 발현에 미치는 영향)

  • Lee, Jung Eun;Cho, Soo-Muk;Kim, Jin;Kim, Jung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.10
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    • pp.1552-1559
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    • 2013
  • Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

The Effect of Insulin-Like Growth Factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) on Cellular Proliferation in Mouse 3T3 Fibroblast Cells (마우스 섬유아세포(3T3 fibroblast cells)에서 Insulin-like Growth Factor-I(IGF-I) 및 IGF Binding Protein-3 (IGFBP-3)이 세포증식에 미치는 영향)

  • Cho, Chul-Ho;Kwak, Seung-Min;Moon, Tae-Hun;Cho, Jae-Hwa;Ryu, Jeong-Seon;Lee, Hyong-Lyeol
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.5
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    • pp.618-628
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    • 1999
  • Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.

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Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

  • Baek, Ae Rin;Lee, Ji Min;Seo, Hyun Jung;Park, Jong Sook;Lee, June Hyuk;Park, Sung Woo;Jang, An Soo;Kim, Do Jin;Koh, Eun Suk;Uh, Soo Taek;Kim, Yong Hoon;Park, Choon Sik
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.3
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    • pp.143-152
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    • 2016
  • Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.