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PKCβ Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3β

  • Shin, Jihye;Jang, Hyunduk;Lin, Jingjing;Lee, Soo Young
    • Molecules and Cells
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    • 제37권10호
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    • pp.747-752
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    • 2014
  • Protein kinase C (PKC) family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. However, the role of PKC in receptor activator of NF-${\kappa}B$ ligand (RANKL) signaling has remained elusive. We now demonstrate that $PKC{\beta}$ acts as a positive regulator which inactivates glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and promotes NFATc1 induction during RANKL-induced osteoclastogenesis. Among PKCs, $PKC{\beta}$ expression is increased by RANKL. Pharmacological inhibition of $PKC{\beta}$ decreased the formation of osteoclasts which was caused by the inhibition of NFATc1 induction. Importantly, the phosphorylation of GSK-$3{\beta}$ was decreased by $PKC{\beta}$ inhibition. Likewise, down-regulation of $PKC{\beta}$ by RNA interference suppressed osteoclast differentiation, NFATc1 induction, and GSK-$3{\beta}$ phosphorylation. The administration of PKC inhibitor to the RANKL-injected mouse calvaria efficiently protected RANKL-induced bone destruction. Thus, the $PKC{\beta}$ pathway, leading to GSK-$3{\beta}$ inactivation and NFATc1 induction, has a key role in the differentiation of osteoclasts. Our results also provide a further rationale for $PKC{\beta}$'s therapeutic targeting to treat inflammation-related bone diseases.

암수동체 어류 점박이송사리 Rivulus marmoratus (Cyprinodontiformes, Rivulidae) β-Actin 2 유전자의 클로닝 및 종내 변이 (Cloning and Intraspecific Variation of β-Actin 2 Gene from the Hermaphroditic Fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae))

  • 정상운;이영미;이창주;이재성
    • 한국어류학회지
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    • 제17권1호
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    • pp.49-56
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    • 2005
  • 점박이송사리, Rivulus marmoratus에서 기원된 16개의 ${\beta}-actin$ 유전자의 염기서열 분석 결과 1,764~1,769 bp 범위를 가지는 ${\beta}-actin$ 유전자를 분리하였다. 이는 기존에 보고된 점박이송사리 ${\beta}-actin$ 유전자와 exon 1 및 intron 2지역에서 다소의 차이를 보여 우리는 이를 점박이송사리 ${\beta}-actin$ 2 유전자라 명명하였다. Multiple alignment를 이용하여 유전자 서로간의 차이를 비교한 결과, 점박이송사리 ${\beta}-actin$ 유전자는 variation을 볼 수 있었다. 따라서 본 연구에서는 점박이송사리에 있어 ${\beta}-actin$ 유전자의 종내 변이 (intraspecific variation)를 확인하였다.

DNA topoisomerase I 억제제 β-lapachone에 의한 전립선 암세포의 성장억제 기전연구 (Up-regulation of Bax is associated with DNA topoisomerase I inhibitor β-lapachone-induced apoptosis in human prostate carcinoma cells)

  • 공규리;최병태;최영현
    • 생명과학회지
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    • 제12권4호
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    • pp.469-476
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    • 2002
  • 남미지역에 서식하는 Tabebuia avellanedae의 수피에서 동정된 천연 quinone계 물질인 $\beta$-lapachone은 DNA topoisomerase I 억제제 이외 다양한 약리학적 기능이 있을 것으로 추정되지만 그 기능이 명확하지 않다. $\beta$-lapachone의 생리활성 기전 해석의 일환으로 본 연구에서는 인체 전립선 DU-145 암세포주의 성장에 미치는 $\beta$-lapachone의 영향을 조사하였다. p-lapachone이 함유된 배지에서 자란 암세포들은 $\beta$-lapachone 처리 농도 의존적으로 성장이 억제되었으며, 이는 apoptosis가 유발된 세포에서 특징적으로 관찰되는 chromatin condensation 및 DNA fragmentation 현상을 유발하였고, DNA flow cytometry 분석결과 apoptotic-sub Gl기에 해당하는 세포들의 빈도도 증가되었다. 또한 poly (ADP-ribose) polymerase 및 $\beta$-catenin 단백질의 발현에서도 apoptosis 유발 특이적인 분해 현상을 보여주었으며, DU-145 전립선 암세포에서 $\beta$-lapachone에 의한 이러한 apoptosis의 유발에는 Bax의 발현증가에 따른 Bcl-2 발현의 감소가 중요한 역할을 할 고 있는 것으로 사료된다.

초임계 이산화탄소를 이용한 2-Hydroxypropyl-β-Cyclodextrin 미립자와 이부프로펜과의 포접복합체 제조 (Utilization of Supercritical Carbon Dioxide for the Preparation of 2-Hydroxypropyl-β-Cyclodextrin Microparticles and Their Inclusion Complexes with Ibuprofen)

  • 유종훈
    • 청정기술
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    • 제19권3호
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    • pp.212-218
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    • 2013
  • 초임계 이산화탄소를 역용매로 이용하는 aerosol solvent extraction system (ASES) 방법을 사용하여 HP-${\beta}$-CD 미립자를 제조하였으며, 공정변수가 입자의 크기와 형태에 미치는 영향을 조사하였다. 또한, 초임계 이산화탄소를 이용하여 이부프로펜과 HP-${\beta}$-CD의 포접복합체를 제조하였으며, ASES 공정에 의해 변형된 HP-${\beta}$-CD의 입자 형상이 포접효율에 미치는 영향에 대해 고찰하였다. ASES 공정으로 제조된 HP-${\beta}$-CD 미립자는 50~200 nm 크기의 나노 입자들이 응집된 입자 형상을 나타내었다. 에탄올 수용액을 HP-${\beta}$-CD의 용매로 사용한 경우 구형의 입자가 제조되었으며, 물의 양이 증가함에 따라 입자의 크기가 증가하였다. 초임계 이산화탄소를 이용해 고체상태에서 이부프로펜/HP-${\beta}$-CD 포접복합체를 제조하는 경우 초임계 ASES 방법에 의한 미세입자화 공정을 통해 포접효율을 향상시킬 수 있는 가능성을 확인하였다.

부산지역 하천에서 분리된 장내세균 Escherichia coli와 Klebsiella pneumoniae의 광범위 베타 락탐 분해효소 (Extended-Spectrum ${\beta}-Lactamase$)에 대한 유형별 분류 (Typing of Extended-Spectrum ${\beta}-Lactamase$ of Escherichia coli and Klebsiella pneumoniae Isolated from Rivers in Busan, Korea)

  • 이훈구;김혜진;김군도
    • 미생물학회지
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    • 제43권2호
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    • pp.116-123
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    • 2007
  • 본 연구는 부산지역 하천에서 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소(extended spectrum ${\beta}-lactamase;\;ESBL$)를 생성하는 세균을 분리하여 생성된 광범위 ${\beta}-lactam$ 분해효소를 유형별로 분류하기 위함이다. Escherichia coli 6균주와 Klebsiella pneumoniae 15균주가 피전달균주인 Escherichia coli J53 $Azid^{R}$에 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소 생성 인자를 전달하였다. PCR 후 얻은 유전인자를 plasmid로 매개된 광범위 ${\beta}-lactam$ 분해효소 유전자의 염기서열 분석결과, E. coli와 K. pneumoniae 유전자를 BCM Search Launcher 및 GenBank nucleotide database를 통하여 검색한 결과 ESBL 유형은 TEM-52형과 SHV-12형이었다. TEM-52는 E. coli와 K. pneumoniae 양쪽에서 분리되었다. 그러나 SHV-12는 K. pneumoniae에서만 분리되었다. 이상의 결과로부터 plasmid 매개성 광범위 ${\beta}-lactam$ 분해효소를 생성하는 세균이 한국에서는 이미 임상범위를 넘어 자연계까지 확산되었음을 알 수 있었다.

Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells

  • Jeong, Da Eun;Heo, Sungeun;Han, Ji Hye;Lee, Eun-young;Kulkarni, Rohit N.;Kim, Wook
    • Molecules and Cells
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    • 제41권10호
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    • pp.909-916
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    • 2018
  • In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

고지방식이와 streptozotocin으로 유도된 당뇨 생쥐에서 β-glucan이 첨가된 보리숙면의 혈당조절과 면역력증진 효과 (Blood Glucose Control and Increase Immunity Effects of β-glucan added Cooked Barley Noodle in High-Fat Diet and Streptozotocin-Induced Diabetic Mice)

  • 박충무;윤현서
    • 대한통합의학회지
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    • 제6권2호
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    • pp.89-98
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    • 2018
  • Purpose : This study was designed to examine the blood glucose control and increase immunity effects of ${\beta}-glucan$ added cooked barley noodle in streptozotocin-induced diabetes mice with a high-fat diet. Method : Forty-eight male ICR mice (6-week-old) were fed AIN-93 diet for 4 weeks. Mice were divided into six groups: normal, diabetic, cooked barley noodle, ${\beta}-glucan$ (5 %) control and two experimental groups (${\beta}-glucan$ 2.5 % and 5 %, cooked barley noodle contained diet with ${\beta}-glucan$ 2.5 % and 5 % w/w). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (150 mg/kg). Result : Blood glucose level was significantly decreased in groups consuming cooked barley noodles, but no significant difference was exhibited in diabetic and ${\beta}-glucan$ control group. These results were in accordance with the result of oral glucose tolerance test. Blood interfereon $(IFN)-{\gamma}$ was measured in order to identify increase immunity effect of ${\beta}-glucan$ in diabetic mice. Inhibited $IFN-{\gamma}$ concentration was recovered in cooked barley noodle and ${\beta}-glucan$ control group. Moreover, $IFN-{\gamma}$ concentration was dramatically elevated in ${\beta}-glucan$ contained cooked barley noodle groups in a dose dependent manner. Streptozotocin induced AST and ALT activities were decreased in ${\beta}-glucan$ contained cooked barley noodle groups with a strong lipid lowering effect. Conclusion : Although addition of ${\beta}-glucan$n did not give any significant synergistic effect on cooked barley noodle in blood glucose regulation, suppressed $IFN-{\gamma}$ production by STZ was dramatically enhanced by ${\beta}-glucan$ supplementation in a dose dependent manner. Liver function and blood lipid profile were also in accordance with the increase immunity effect of ${\beta}-glucan$. Consequently, ${\beta}-glucan$ added cooked barley noodle can be consumed as good diets for patients with chronic diseases with reduced immunity.

$\beta-Glucan$ 첨가 Pound Cake의 이화학적$\cdot$관능적 특성 (Physicochemical Characteristics of Pound Cake Added with $\beta-Glucan$)

  • 신유미;김미경;조한영;김미리
    • 동아시아식생활학회지
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    • 제15권6호
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    • pp.728-737
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    • 2005
  • This study was conducted to evaluate the physicochemical characteristics of pound cake made of substituted flour with different amount of $\beta-glucan$ i.e. 3, 6 and $9\%$ respectively. $\beta-glucan$ is a functional food material produced from Agrobacterium sup. R259 KCTC 10197BP. The specific gravity and pH of dough were found to be increased according to $\beta-glucan$ content Rheological property such as adhesiveness of dough has no difference between control and $\beta-glucan$ added groups. The pH of baked pound cake was not significantly different between control and $\beta-glucan$ groups. The volume of baked pound cake wag not significantly different between control and the ones with up to $6\%$ $\beta-glucan$, Lightness (L), redness (a) and yellowness (b) value of Hunter color system of cake crumb were not significantly different among teated groups, except a value of crust in $9\%$ $\beta-glucan$ group. the moisture content of cake increased according to $\beta-glucan$ content. Hardness by texture analyser was decreased with increasing $\beta-glucan$ content although cohesiveness wag not changed in β$\beta-glucan$ groups, compared with the control. Sensory evaluation results showed that the mean scores of over·all acceptability in 3 and $6\%$ $\beta-glucan$ were higher than that of control. Based on these results, the addition of $\beta-glucan$ to pound cake up to $6\%$ was considered to be desirable especially in terms of texture.

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The PPLA Motif of Glycogen Synthase Kinase 3β Is Required for Interaction with Fe65

  • Lee, Eun Jeoung;Hyun, Sunghee;Chun, Jaesun;Shin, Sung Hwa;Lee, Kyung Eun;Yeon, Kwang Hum;Park, Tae Yoon;Kang, Sang Sun
    • Molecules and Cells
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    • 제26권1호
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    • pp.100-105
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    • 2008
  • Glycogen synthase kinase $3{\beta}$ (GSK $3{\beta}$) is a serine/threonine kinase that phosphorylates substrates such as ${\beta}$-catenin and is involved in a variety of biological processes, including embryonic development, metabolism, tumorigenesis, and cell death. Here, we present evidence that human GSK $3{\beta}$ is associated with Fe65, which has the characteristics of an adaptor protein, possessing a WW domain, and two phosphotyrosine interaction domains, PID1 and PID2. The GSK $3{\beta}$ catalytic domain also contains a putative WW domain binding motif ($^{371}PPLA^{374}$), and we observed, using a pull down approach and co-immunoprecipitation, that it interacts physically with Fe65 via this motif. In addition, we detected co-localization of GSK $3{\beta}$ and Fe65 by confocal microscopy, and this co-localization was disrupted by mutation of the putative WW domain binding motif of GSK $3{\beta}$. Finally, in transient transfection assays interaction of GSK $3{\beta}$ (wt) with Fe65 induced substantial cell apoptosis, whereas interaction with the GSK $3{\beta}$ AALA mutant ($^{371}AALA^{374}$) did not, and we noted that phosphorylation of the Tyr 216 residue of the GSK $3{\beta}$ AALA mutant was significantly reduced compared to that of GSK $3{\beta}$ wild type. Thus, our observations indicate that GSK $3{\beta}$ binds to Fe65 through its $^{371}PPLA^{374}$ motif and that this interaction regulates apoptosis and phosphorylation of Tyr 216 of GSK $3{\beta}$.

Chlorinated Polyolefine (CPO)-g-β Carboxy Ethyl Acid (β-CEA) 수지의 합성 및 이를 Base Polymer로 하는 프라이머의 제조 및 물성 (Preparation and Characterization of Primer and Synthesized Chlorinated Polyolefine (CPO)-g-Carboxy Ethyl Acid (β-CEA))

  • 정부영;천정미;오상택;김태균;천제환
    • 접착 및 계면
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    • 제12권2호
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    • pp.62-66
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    • 2011
  • 본 연구에서는 PP (Polypropylene) 수지에 접착력이 우수한 저유해성 프라이머를 제조하기 위하여, 라디칼 중합법을 사용하여 $\beta$-carboxy ethyl acid ($\beta$-CEA)가 그라프트 중합된 Chlorinated Polyolefine (CPO)을 합성하였다. 또한 합성된 CPO-g-$\beta$-CEA를 이용하여, PP용 프라이머를 제조하고 유해성과 접착특성을 살펴보았다. 합성된 CPO-g-$\beta$ CEA의 구조 및 특성을 알아보기 위하여 FT-IR, DSC, UTM을 사용하였으며, 그라프트율은 $\beta$-CEA를 5 wt% 사용하였을 때 최적으로 나타났다. 또한 합성된 CPO-g-$\beta$-CEA에 접착증진제인 PX-95를 함량별로 사용하여 PP용 프라이머를 제조하고 접착력을 평가한 결과, 접착증진제의 함량이 3 wt%인 경우 접착력이 4.0 kgf/cm로 가장 높게 나타났다.