• 제목/요약/키워드: PDE

검색결과 320건 처리시간 0.029초

PDE 저해제에 의한 $PGE_2$의 파골세포 분화 유도 증강효과 (The Stimulatory Effect of PDE Inhibitors on $PGE_2$-Induced Osteoclastogenesis)

  • 노아롱새미;임미정
    • 약학회지
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    • 제51권4호
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    • pp.235-238
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    • 2007
  • To determine the regulatory roles of phosphodiesterase (PDE) inhibitors on $PGE_2$-induced osteoclastogenesis, we investigated the effect of PDE inhibitors on osteoclast formation in the presence of $PGE_2$. Among PDE isozyme specific inhibitors, milrinone, a selective PDE3 inhibitor, and rolipram, a specific PDE4 inhibitor, increased $PGE_2$-induced osteoclast formation in cocultures of mouse bone marrow cells and osteoblasts. To verify that whether the PDE3 and PDE4 inhibitors act indirectly on osteoblasts, we measured the concentration of intracellular cAMP in osteoblasts. Treatment of milrinone or rolipram increased $PGE_2$-stimulated cAMP levels in osteoblasts. Furthermore, northern blot analysis revealed that the PDE3 and PDE4 inhibitors works synergistically with $PGE_2$ to increase the expression of TRANCE mRNA in osteoblasts. On the contrary, the PDE3 and PDE4 inhibitors did not augment the number of osteoclasts differentiated from bone marrow cells by $PGE_2$. In conclusion, the stimulation of $PGE_2$-induced osteoclast formation by the PDE3 and PDE4 inhibitors are attributable to their indirect effect on osteoblasts, not to their direct effect on bone marrow-derived osteoclast precursors.

조골세포내 PDE4에 의한 PTH 신호의 음성적 조절 (The Negative Role of PDE4 on PTH-induced Signaling in Osteoblasts)

  • 박효정;노아롱새미;이정민;임미정
    • 약학회지
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    • 제54권5호
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    • pp.410-415
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    • 2010
  • We explored the role of phosphodiesterase 4 (PDE4) on parathyroid (PTH)-induced signaling in osteoblasts. PTH was shown to increase the activity of PDE, mainly PDE4, in osteoblasts, which is partly attributable to elevated PDE4B and PDE4D mRNA expression. The use of PDE4 inhibitor strengthened the PTH-induced extracellular signal-regulated kinase (ERK) and p38 MAP kinase (MAPK) activation. Furthermore, the PDE4 inhibitor stimulated PTH-induced receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) expression in osteoblasts, which in turn increased osteoclast formation. Taken together, these data suggest the negative role of PDE4 on PTH-induced signaling in osteoblasts.

Selective Inhibitory Effect of New Phosphodiesterase Inhibitors on PDE Isozymes in Guinea pig Cardiac Muscle

  • Lee, Sun-Kyeong;Kwon, Kwang-Il;Zee, Ok-Pyo
    • Archives of Pharmacal Research
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    • 제12권4호
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    • pp.276-281
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    • 1989
  • Selective inhibition of seven new PDE inhibitors on cyclic nucleotide PDE isozymes was investigated. Three PDE isozymes (PDE I, II and III) of guinea pig left ventricular muscles were used. All tested agents inhibited cyclic AMP hydrolysis by PDE III IN A concentration-dependent manner. Some agents represented more potent and selective inhibitory effect on PDE III than that of imazodan.

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원형질막 타기팅에 필요한 ApPDE4의 N-말단의 아미노산 서열 분석 및 발현에 의한 형태적 변화 (Identification of N-terminal amino acids of ApPDE4 involved in targeting to plasma membrane and cellular morphological change by expression of N-terminal peptide)

  • 김건형;전용우;이진아;장덕진
    • 분석과학
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    • 제26권1호
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    • pp.106-112
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    • 2013
  • Phosphodiesterase (PDE)는 세포내의 cAMP를 분해하는 효소로 세포의 신호 전달에 중요한 기능을 수행하는 것으로 알려져 왔다. 각각의 PDE들은 N-말단의 서열을 통해 세포 내 특정 부위로 이동되어 기능을 수행한다. 이전의 연구를 통해 바다달팽이인 군소에서 새롭게 클로닝된 ApPDE4 long-form이 원형질막과 시냅스전 뉴런의 말단에 발현됨을 확인하였다. 그러나, 현재까지 이러한 세포내 작용부위로의 이동, 즉 타겟팅(targeting)에 필요한 최소부위가 어디인지, 이러한 타겟팅이 세포에 미치는 영향은 무엇인지는 보고되지 않았다. 따라서, 본 연구에서는 이를 알아보기 위해 첫째, 원형질막으로 타겟팅에 필요한 최소부위를 알아 보고자 하였다. 이를 위해 다양한 결실돌연변이체를 제작하고, 이들의 이동과 분포를 확인한 결과, N-말단 13개의 아미노산만으로도 원형질막으로 타기팅에 충분하다는 것을 확인할 수 있었다. 또한, ApPDE4 N-말단의 20개 아미노산을 mRFP에 융합해서 만든 ApPDE4(N20)-mRFP를 HEK293T 세포에 과발현시킨 결과, 기포(bleb)가 생성되는 세포의 비정상적인 형태 변화가 관찰 되었다. 이러한 형태적 변화는 ApPDE4가 원형질막으로 타겟팅되는 것과 관련이 있었다. 대표적인 인지질의 하나인 PI4,$5P_2$에 선택적으로 결합함으로써 원형질막으로 타겟팅되는 단백질인 mRFP-$PLC{\delta}1$(PH)의 과발현도 ApPDE4(N20)-mRFP와 비슷한 세포의 형태적 변화가 유도됨을 확인할 수 있었다. ApPDE4의 N-말단은 PI4,$5P_2$와 같은 인지질과의 결합으로 원형질막으로 타겟팅될 수 있고, 형태적 변화를 유도하는 가능성을 제시한다.

블록 정합오차 예측을 이용한 고속 PDE 알고리즘 (Fast PDE Algorithm Using Block Matching Error Prediction)

  • 신세일;오정수
    • 한국통신학회논문지
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    • 제32권4C호
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    • pp.396-400
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    • 2007
  • 본 논문은 고속 PDE 알고리즘을 제안한다. 기존 PDE 알고리즘이 부분 정합오차를 이용해 후보블록의 나머지 정합 과정을 생략할 수 없을 때 제안된 알고리즘은 계산된 부분 정합오차로부터 예측된 블록 정합오차를 이용해 다시 한번 나머지 정합 과정을 생략하는 것을 평가한다. 예측된 블록 정합오차는 부분 정합오차보다 항상 크므로 제안된 알고리즘은 기존 PDE보다 일찍 불가능한 후보 블록을 제거할 수 있다. 모의 실험의 결과들은 제안된 알고리즘이 기존 PDE 정도의 화질을 유지하면서 계산량을 크게 줄여주는 것을 보여준다.

Cyclic Nucleotide Phosphodiesterases as Possible Targets for Ginsenosides

  • Lugnler, C.;Kim, N.D
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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    • pp.216-223
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    • 1998
  • Cyclic nucleotide phosphodiesterases (PDEs) represent the unique enzymatic system degrddinf cAMP and cGMP which play a major role in the regulation of cell physiology. To investigate a possible molecular mechanism of ginsenosides, their activities were evaluated on PDEs which are recently described is new therapeutic targets. PDEs are classified into 7 families according to their genes (PDEI to PDE7) and are differently distributed in tissues. The IC50 values of ginsenosides were determined on PDEI to PDE 5 chromatographically isolatetl from bovine aorta. The results show that total ginseng saponin extract preferentially inhibits PDE 1 and PDE4 at concentrations nearby 200 ug/ml. Protopanaxadiol (PPD) fraction acts preferentially on PDE4 with and IC50 value of 100 nlml and inhibits also PDEI and PDE5 at 14 to 2 fold higher concentrations, respectively. Protopanaxatriol (PPT) fraction preferentially inhibits PDE 1 with and IC50 value of 170 ug/ml. Compound Rgl, originated from PPT fraction, and RC3 (5) represent the most active compounds towards PDE 1 with IC50 values around 80 UM. However Rg3 (R), epimer of Rgl (5) has no effect on the various PDEs tested, excepted on PDE3 rich is sligthly sensitive Compound Rbl, originated from PPD, acts on both PDEI and PDE4. It if two fold less active than Rgl and Rg3 (5) on PDEI. Taken together, these results mainly suggest that PDEI and PDE4 inhibitions could be a molecular mechanism which would participate in ginsenoside mechanisms, especially the effect of PPD on blood vessel and on CNS.

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흰쥐 대동맥에서 cyclic nucleotide phosphodiesterase 억제제들의 혈관 이완 특성 (Vasorelaxant properties of cyclic nucleotide phosphodiesterase inhibitors in rat aorta)

  • 강형섭;최철호;김진상
    • 대한수의학회지
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    • 제43권4호
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    • pp.615-624
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    • 2003
  • Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.

Science Teaching and Learning for Productive Disciplinary Engagement (PDE) through Model-Based Learning (MBL): Insights from Relevant Literature

  • Park, Byung-Yeol;Campbell, Todd
    • 한국지구과학회지
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    • 제43권4호
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    • pp.490-497
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    • 2022
  • The practice turn in the science education community emphasizes students' engagement in the activities that scientists and engineers actually do when they see, explain, and critique a phenomenon, or solve a problem. This turn highlights the importance of science learning environments for students. Consequently, the purpose of this study was the examination of relevant literature with the aim of proposing theoretically and empirically derived teaching strategies for students' productive disciplinary engagement (PDE) through model-based learning (MBL) in science classrooms. To this end, collected literature focusing on PDE and MBL was analyzed to better understand 1) how teachers can foster students' PDE in science classrooms, 2) how PDE can be connected to MBL, and 3) what supports are required for students' PDE through MBL. As a result of our analysis, a close relationship between PDE and MBL was identified. Importantly, this research reveals the promise of MBL for supporting students' PDE through the problematizing, authority, accountability, and resources. Further, our literature examination provided a better understanding of what supports are required for students' engagement in PDE through MBL and why this matters in the context of the practice turn in science education.

GPS Phone 개발 환경 구축을 위한 PDE Emulator 구현 (Development of POE Emulator for GPS Phone Test Environment)

  • 조진근;황진옥;민성기
    • 한국정보과학회:학술대회논문집
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    • 한국정보과학회 2004년도 가을 학술발표논문집 Vol.31 No.2 (3)
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    • pp.61-63
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    • 2004
  • GPS Phone 이 Location Service를 제공하기 위해서는 위성데이터를 GPS Phone 에 제공하는 PDE(Position Determination Entity) 가 필요한데 초기 개발단계에서 실제 PDE를 개발단계의 GPS Phone에 연동하기는 번거롭고 비효율적인 면이 많다. 따라서 실제 PDE를 대신하여 개발단계의 GPS Phone 에 위성데이타를 제공해 줄 SW가 필요하다. 이에 본 논문은 Location Service를 제공하는 GPS Phone 초기 개발단계에서의 시험을 위해 실제 PDE를 대신할 수 있는 PDE Emulator를 구현하였다.

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PDE-PRESERVING PROPERTIES

  • PETERSSON HENRIK
    • 대한수학회지
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    • 제42권3호
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    • pp.573-597
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    • 2005
  • A continuous linear operator T, on the space of entire functions in d variables, is PDE-preserving for a given set $\mathbb{P}\;\subseteq\;\mathbb{C}|\xi_{1},\ldots,\xi_{d}|$ of polynomials if it maps every kernel-set ker P(D), $P\;{\in}\;\mathbb{P}$, invariantly. It is clear that the set $\mathbb{O}({\mathbb{P}})$ of PDE-preserving operators for $\mathbb{P}$ forms an algebra under composition. We study and link properties and structures on the operator side $\mathbb{O}({\mathbb{P}})$ versus the corresponding family $\mathbb{P}$ of polynomials. For our purposes, we introduce notions such as the PDE-preserving hull and basic sets for a given set $\mathbb{P}$ which, roughly, is the largest, respectively a minimal, collection of polynomials that generate all the PDE-preserving operators for $\mathbb{P}$. We also describe PDE-preserving operators via a kernel theorem. We apply Hilbert's Nullstellensatz.