• 제목/요약/키워드: MG-132

검색결과 416건 처리시간 0.026초

Gamma Irradiation Up-regulates Expression of B Cell Differentiation Molecule CD23 by NF-κB Activation

  • Rho, Hyun-Sook;Park, Soon-Suk;Lee, Choong-Eun
    • BMB Reports
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    • 제37권4호
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    • pp.507-514
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    • 2004
  • Gamma irradiation ($\gamma$-IR) is reported to have diverse effects on immune cell apoptosis, survival and differentiation. In the present study, the immunomodulatory effect of a low dose $\gamma$-IR (5~10 Gy) was investigated, focusing on the role of NF-${\kappa}B$ in the induction of the B cell differentiation molecule, CD23/FceRII. In the human B cell line Ramos, $\gamma$-IR not only induced CD23 expression, but also augmented the IL-4-induced surface CD23 levels. While $\gamma$-IR did not cause STAT6 activation in these cells, it did induce both DNA binding and the transcriptional activity of NF-${\kappa}B$ in the $I{\kappa}B$ degradation-dependent manner. It was subsequently found that different NF-${\kappa}B$ regulating signals modulated the $\gamma$-IR-or IL-4-induced CD23 expression. Inhibitors of NF-${\kappa}B$ activation, such as PDTC and MG132, suppressed the $\gamma$-IR-mediated CD23 expression. In contrast, Ras, which potentiates $\gamma$-IR-induced NF-${\kappa}B$ activity in these cells, further augmented the $\gamma$-IR- or IL-4-induced CD23 levels, The induction of NF-${\kappa}B$ activation and the subsequent up-regulation of CD23 expression by $\gamma$-IR were also observed in monocytic cells. These results suggest that $\gamma$-IR, at specific dosages, can modulate immune cell differentiation through the activation of NF-${\kappa}B$, and this potentially affects the immune inflammatory response that is mediated by cytokines.

Downregulation of Cyclin D1 by Sophorae Flos through Proteasomal Degradation in Human Colorectal Cancer Cells

  • Lee, Jin Wook;Park, Gwang Hun;Eo, Hyun Ji;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제28권6호
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    • pp.727-733
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    • 2015
  • Although Sophorae Flos (SF) has been reported to exert an anti-cancer activity, molecular targets and mechanisms associated with anti-cancer activity of SF have been unclear. Because cyclin D1 has been regarded as an important regulator in the cell proliferation, we focused cyclin D1 and investigated the effect of SF on the cyclin D1 regulation in light of elucidating the molecular mechanism for SF’s anti-cancer activity. The treatment of SF decreased cellular accumulation of cyclin D1 protein. However, SF did not change the level of cyclin D1 mRNA. Inhibition of proteasomal degradation by MG132 attenuated SF-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with SF. In addition, a point mutation of threonine-286 to alanine attenuated SF-mediated cyclin D1 downregulation. Inhibition of ERK1/2 by a selective inhibitor, PD98059 suppressed cyclin D1 downregulation by SF. From these results, we suggest that SF-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2. SF-induced proteasomal degradation of cyclin D1 might inhibit proliferation in human colorectal cancer cells. The current study provides information on molecular events for an anti-cancer activity of SF

Induction of Cyclin D1 Proteasomal Degradation by Branch Extracts from Abeliophyllum distichum Nakai in Human Colorectal Cancer Cells

  • Park, Gwang Hun;Park, Jae Ho;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제28권6호
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    • pp.682-689
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    • 2015
  • Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme and aldose reductase. Recently, our group found that branch extracts of A. distichum (EAFAD-B) induce apoptosis through ATF3 activation in human colon cancer cells. However, anti-cancer reagents exert their activity through the regulation of various molecular targets. Therefore, the elucidation of potential mechanisms of EAFAD-B for anti-cancer activity may be necessary. To elucidate the potential mechanism of EAFAD-B for anti-cancer activity, we evaluated the regulation of cyclin D1 in human colon cancer cells. EAFAD-B decreased cellular accumulation of cyclin D1 protein. However, cyclin D1 mRNA was not changed by EAFAD-B. Inhibition of proteasomal degradation by MG132 attenuated EAFAD-B-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with EAFAD-B. In addition, EAFAD-B induced cyclin D1 phosphorylation at threonine-286 and the point mutation of threonine-286 to alanine attenuated EAFAD-B-mediated cyclin D1 proteasomal degradation. Inhibitions of both ERK1/2 by PD98059 and NF-κB by a selective inhibitor, BAY 11-7082 suppressed cyclin D1 downregulation by EAFAD-B. From these results, we suggest that EAFAD-B-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2-dependent NF-κB activation. The current study provides new mechanistic link between EAFAD-B and anti-cancer activity in human colon cancer cells.

한국산(韓國産) 고등(高等) 균류(菌類)의 성분(成分) 연구(硏究)(제41보)(第41報) -Lentinus edodes DMC7 균주(菌株)의 배양(培養) 여액(濾液)의 항암(抗癌) 성분(成分)- (Studies on Constituents of the Higher Fungi of Korea(XLI) -An Antitumor Fraction from the Culture Filtrate of Lentinus edodes DMC7-)

  • 정경수;최응칠;김병각
    • 한국균학회지
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    • 제12권4호
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    • pp.129-132
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    • 1984
  • 한국산 담자균류로부터 새로운 항종양 성분을 개발하기 위하여 표고의 일개 균주인 Lentinus edodes DMC7을 인공배지에서 진탕배양하여 그 균사 배양물을 얻었다. 그중 배양 여액으로부터 수용성 고분자 분획을 분리하여 LF-3라고 명명하였다. LF-3는 ICR 마우스에 이식된 Sarcoma 180세포에 대하여 항암작용을 나타내었으며 그 저지율은 53. 1%였다.

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협조에 어려움을 보이는 장애인 환자에서 전신마취 전 경구 Midazolam 전투약의 효과 분석 (Premedication of Oral Midazolam for Smooth Anesthesia Induction of Uncooperative Patients)

  • 이승화;서광석;신터전;김현정;한효조;장주혜
    • 대한치과마취과학회지
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    • 제11권2호
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    • pp.125-132
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    • 2011
  • Background: Adult patients with intellectual disabilities often strongly resist the anesthetic administration for dental procedures. This study aimed to evaluate the effect of midazolam premedication in improving the cooperation level of patients who are likely to be combative and irritated during general anesthesia (GA) induction. Methods: The patients who had received dental treatment under ambulatory GA for more than two times were included. And we selected 13 patients total that needed physical restraint or ketamine IM prior to induction at the first GA, and were prescribed midazolam tablet (7.5-15 mg) at the following GA. We reviewed pre-anesthetic records and anesthesia records, and evaluated cooperative levels of patients (4 levels scale) during anesthesia induction and recovery time retrospectively. Results: All 13 patients (Male 11, Female 2) had severe mental disabilities. The average age of the patients was 24 ${\pm}$ 7 (13-37) years and their average weight was 58 ${\pm}$ 16 (34-91) kg. At the first GA, 10 patients needed physical restraint prior to induction (level 3). And 3 patients were so poorly cooperative that the induction procedure was performed after intramuscular injection of ketamine (level 4). But after the midazolam intake, 7 patients were willing to receive the anesthetic induction (level 1, 2), and 6 patient needed physical restraint (P < 0.05). There were no statistical differences in the duration of general anesthesia and postoperative recovery. Conclusions: Oral intake of midazolam was effective in improvement of cooperation without any complications.

Feasibility of Early and Repeated Low-dose Interscalene Brachial Plexus Block for Residual Pain in Acute Cervical Radiculopathy Treated with NSAIDS

  • Iwata, Toshio;Mitoro, Mari;Kuzumoto, Naoya
    • The Korean Journal of Pain
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    • 제27권2호
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    • pp.125-132
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    • 2014
  • Background: To improve residual pain management in acute cervical radiculopathy treated with NSAIDs, the feasibility of early and repeated low-dose interscalene brachial plexus block (IS-BPB) needs to be assessed. Methods: This was a prospective study on patients receiving NSAIDs (loxoprofen) for cervical radiculopathy of ${\leq}2$-week onset. Pain was assessed using the visual analogue scale (VAS). A low-dose ultrasonography (USG)-guided IS-BPB (dexamethasone [1.65 mg; 0.5 ml] and mepivacaine [1%; 3.0 ml]) was performed at baseline and weekly thereafter for 4 weeks in an outpatient setting for the intervention group. All patients were evaluated using a visual satisfaction score (VSS) at week 4. Patients with baseline VAS scores < 70 (mild to moderate pain; MM group) and ${\geq}70$ (severe pain; SE group) were compared to the controls receiving NSAIDs. Results: A total of 316 IS-BPBs were performed in the intervention group. There was a significant difference in the decline in the VAS from week 0 to week 3 in the MM and SE groups (P < 0.05); however, from week 3 to week 4, the therapeutic effect exhibited no significant difference. Thirteen patients at week 2 (15.5%; MM: 27.7%; SE: 0%), 43 at week 3 (51.2%; MM: 83.0%; SE: 10.8%), and 47 at week 4 (56.0%; MM: 85.1%; SE: 18.9%) achieved a VAS score of ${\leq}20$. Patient satisfaction was high, and the decrease in VAS scores in both groups was significant (P < 0.05) compared to the controls. Conclusions: Weekly, low-dose, USG-guided IS-BPB can be implemented for early pain relief in acute cervical radiculopathy, with high patient satisfaction.

Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells

  • Song, Hun Min;Park, Gwang Hun;Eo, Hyun Ji;Lee, Jin Wook;Kim, Mi Kyoung;Lee, Jeong Rak;Lee, Man Hyo;Koo, Jin Suk;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • 제23권4호
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    • pp.339-344
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    • 2015
  • Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

게르마늄 수용액으로 재배한 콩나물의 항돌연변이 효과 (Antimutagenicity of Soybean Sprouts Cultured with Germanium)

  • 김은정;이경임;박건영
    • 한국식품영양과학회지
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    • 제33권6호
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    • pp.930-935
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    • 2004
  • Ames test와 SOS chromotest를 이용하여 유기 게르마늄과 게르마늄을 첨가하여 재배한 콩나물의 항돌연변이 효과를 검토하였다. 균주 Salmonella typhimurium TA100에서 AFB$_1$에 의하여 유발된 돌연변이는 Ge-132와 게르마늄 가루에 의하여 농도 의존적으로 저해 효과가 높게 나타났으며, 특히 유기 게르마늄을 20 mg/plate 첨가하였을 때 대조군에 비하여 87%의 돌연변이 유발 억제율을 나타내었다. 똑같은 실험계에서 게르마늄을 첨가하여 재배한 콩나물의 즙액과 methanol 추출물은 수돗물로 재배한 콩나물에 비하여 돌연변이 유발억제 작용이 유의적으로 높게 나타났다. 또한 직접돌연변이원인 MNNG와 4-NQO에 의해 유발된 돌연변이는 일반콩나물의 즙액을 200 $\mu$L/plate 첨가하였을 때 각각 37∼39%, 38∼48%의 저해효과를 나타낸 반면 같은 농도에서 게르마늄 콩나물의 즙액은 61%와 75%의 억제율을 나타내어 게르마늄 첨가 콩나물은 간접 돌연변이원뿐만 아니라 직접 돌연변이원에 의해서 유발된 돌연변이도 억제함을 알 수 있었다. 한편 E. coli PQ37 균주를 사용한 SOS chromotest에서 유기 게르마늄은 사용된 농도의 증가에 따라 돌연변이 유발억제작용이 증가하였으며, 게르마늄 콩나물의 methanol 추출물은 일반 콩나물에 비하여 높은 돌연변이 유발 억제작용을 나타내었다. 따라서 Ames test와 SOS chromotest를 통하여 게르마늄을 첨가하여 재배한 콩나물은 수돗물로 재배한 콩나물에 비하여 항돌연변이 효과가 우수한 것을 알 수 있었다.

p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages

  • Aziz, Nur;Kim, Eunji;Yang, Yanyan;Kim, Han Gyung;Yu, Tao;Cho, Jae Youl
    • BMB Reports
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    • 제55권8호
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    • pp.389-394
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    • 2022
  • In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E2 (PGE2) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE2 secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs.

Morphological characters, Total phenolic content, and Fatty Acid Compositions of Safflower (Carthamus tinctorius) Genetic Resources

  • Awraris Derbie Assefa;Young Jee Kim;Ae-Jin Hwang;Bich-Saem Kim;Jae-Eun Lee
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2020년도 춘계학술대회
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    • pp.94-94
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    • 2020
  • Safflower, a draught and salt tolerant oil seed crop of Compositae family, has been cultivated around the world mainly as source of edible oils and dyes, where India, the USA, Mexico, Australia, and Ethiopia contributing about 85% of the production altogether. In this study we have characterized some selected morphological properties of safflower plant and determined the the total phenolic content (TPC) and fatty acid composition in seeds of 237 genetic resources. All the seed coats were white colored while the petals had red, yellow and white pigments. The yellow was the predominant petal color being recorded in 182 accessions followed by red occurring in 49 accessions. The petal color of 47 of the accessions changed with development while the 190 accession showed no change of color. The leaves are ovate to obovate, mostly with dentate (21 moderate and 205 weak) and few smooth (11) margins. The plant length, leaf length, and leaf width were ranged between 65.7 and 160.8 cm, 14.3 and 37.0 cm, and 3.3 and 12.1 cm, respectively. The TPC was determined using Folin-Ciocalteu method and fatty acid compositions were evaluated using gas chromatography. The TPC content ranged from 23.71 to 132.72 µgGAE/mg dried extract (DE). The seeds of safflower genetic resources accounted an average crude fat content of 26.25% (14.84 to 41.70%). The total fatty acid is mainly comprised of 71.72% linoleic acid (18:2) and 20.08% oleic acid (18:1) on average, the remaining palmitic acid (16:0), stearic acid (18:0) and linolenic acid (18:3) contributing 5.84, 2.23 and 0.15 %, respectively. The fatty acid composition of safflower seeds has shown great variability, where oleic and linoleic acid have a wide range of variation, from 9.23 to 83.35% and from 10.46 to 82.62%, respectively

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