P-I-OPEN MAPPINGS, P-I-CONTINUOUS MAPPINGS AND P-I-IRRESOLUTE MAPPINGS

김지윤,김창수 한국수학교육학회 2009 純粹 및 應用數學 Vol.16 No.4

The notions of P-I-open (closed) mappings, P-I-continuous mappings, P-I-neighborhoods, P-I-irresolute mappings and I-irresolute mappings are intro-duced. Relations between P-I-open (closed) mappings and I-open (closed) map-pings are given. Characterizations of P-I-open (closed) mappings are provided. Relations between a P-I-continuous mapping and an I-continuous mapping are discussed, and characterizations of a P-I-continuous mapping are considered. Con-ditions for a mapping to be an I-irresolute mapping (resp. P-I-irresolute mapping)are provided.

A study on the regulatory effect of p-38 MAP kinase on nitric oxide and interleukin-6 in osteoblasts

Lee, Kyung-Won,Lee, Doe-Hoon,Kang, Kyung-Hwa,Kim, Sang-Cheol 대한치과교정학회 2003 대한치과교정학회지 Vol.33 No.3

치아이동 시 발생하는 골흡수에서 이미 여러 cytokine의 중요성이 강조된 바 있으며 이 가운데 interleukin-6는 구강 및 연골조직 등에서 많은 연구의 초점이 되어 왔으나 확실한 기전은 아직까지 정확ㅚ 확립되어 있지 못하다. 골흡수 시조골세포에서 유리되는 , Interleukn-6 (IL-6)와 nitric oxide(NO) 등이 골흡수의 조절자로 최근 대두되고 있으며 Mitogen-activated protein kinase (MAPK)의 활성화로 인해 염증성 cytokine등이 유리될 수 있음이 최근 macrophage 등에서 증명된 바 있다. 그러므로 치아이동을 비롯한 구강 내 여러 염증의 조건에서 골흡수의 대표인자인 IL-6 및 NO 유리가 MAPK 등의 활성 등을 통해 조절될 수 있는 가능성을 시사하고 있다. 본 연구에서 조골세포 특징을 대부분 가지고 있는 조골세포주, MC3TE1에서 p-38 MAP kinase을 매개로 NO와 IL-6가 유리됨을 확인하고자 하였다. 10% Fetal Bovine Serum이 첨가된 -MEM 배양액으로 배양한 조골세포주인 MC3TE1 세포에 tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) 및 lipopolysacchalide(LPS)등의 단독처리 시 NO와 IL-6의 증가는 확인되지 않았으나 TNF-α/IFN-γ 혹은 LPS/IFN-γ 등의 처치시 NO와 IL-6의 유의한 증가를 보였으며, NO 발현에 직접 관여하는 inducible nitric oxide synthase (iNOS)와 IL-6 단백질 및 mRNA의 발현을 관찰하였다. 또한 specific p=38 MAP kinase inhibitor 인 SB203580의 NO와 IL-6의 생성을 조절하고 있음을 시사하여 주고 있다. TNF-α/IFN-γ 혹은 LPS/IFN-γ 처치시 p-38 MAP Kinase의 활성을 관찰하였으나 단독 처치 시 역시 p-38 MAP Kinase의 활성을 확인함으로써 NO와 IL-6생성기전에는 p-38 MAP Kinase이외에 다른 인자 역시 관여하고 있음을 보여주고 있다. 본 연구에서는 치아 등의 골조직의 구성 세포인 조골세포에서 NO와 IL-6유리를 확인하였으며, 또한 이들의 생성기전중의 하나로 p-38 MAP Kinase가 transcription 단계에서 관여하고 있음을 확인하였다. Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(Ⅱ-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the releas of the inflammatory cytokines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined interferon-γ(IFN-γ), lipopolysaccharide (LPS) and tumor necrosis factor-α(TNF-α) induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, IFN-γ,LPS, and TNF-α individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents- Stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were sighnificantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p38 MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in LPS/IFNγ-or TNF-α/IFN-γ treated MC3T3E-1 osteoblasts.

Interaction of Microtubule-associated Protein 1B Light Chain(MAP1B-LC1) and p53 Represses Transcriptional Activity of p53

Kim, Jung-Woong,Lee, So-Youn,Jeong, Mi-Hee,Jang, Sang-Min,Song, Ki-Hyun,Kim, Chul-Hong,Kim, You-Jin,Choi, Kyung-Hee The Korean Society for Integrative Biology 2008 Animal cells and systems Vol.12 No.2

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and can trigger apoptosis in many cell types including neurons. In this study, we have shown that Microtubule-associated protein 1B(MAP1B) light chain interacts with tumor suppressor p53. MAP1B is one of the major cytoskeletal proteins in the developing nervous system and essential in forming axons during elongation. We also demonstrate that both p53 and MAP1B-LC1 interact in the nucleus in HEK 293 cells. Indeed, we show that the MAP1B-LC1 negatively regulates p53-dependent transcriptional activity of a reporter containing the p21 promoter. Consequently, MAP1B light chain binds with p53 and their interaction leads to the inhibition of doxorubicin-induced apoptosis in HEK 293 cells. Furthermore, these examinations might be taken into consideration when knock-down of MAP1B-LC1 is used as a cancer therapeutic strategy to enhance p53's apoptotic activity in chemotherapy.

조골세포에서 p-38 MAP kinase의 nitric oxide 및 interieukin-6 생성조절에 관한 연구

이경원(Kyung-Won Lee),이도훈(Doe-Hoon Lee),강경화(Kyung-Hwa Kang),김상철(Sang-Cheol Kim) 대한치과교정학회 2003 대한치과교정학회지 Vol.33 No.3

치아이동 시 발생한는 골흡수에서 이미 여러 cytokine의 중요성이 강조된 바 있으며 이 가운데 intreleukin-6는 구강 및 연골조직 등에서 많은 연구의 초점이 되어 왔으나 확실한 기전은 아직까지 정확히 확립되어 있지 못하다. 골흡수 시조골세포에서 유리되는 Interleukin-6 (IL-6)와 nitric oxide (NO) 등이 골흡수의 조절자로 최근 대구되고 있으며 Mitogen-activated protein kinase (MAPK)의 활성화로 인해 염증성 cytokine등이 유리될 수 있음이 최근 macropage등이 증명된 바 있다. 그러므로 치아이동을 비롯한 구강 내 여러 염증의 조건에서 골흡수의 대표인자 IL-6및 NO 유리가 MAPK등의 활성 등을 통해 조절된 수 있는 가능성을 시사하고 있다. 본 연구에서 조골세포 특징을 대부분 가지고 있는 조골세포주, MC3T3E1에서 p-38 MAP kinase을 매개로 NO 와 IL-6가 유리됨을 확인하고자 하였다. 10% Fetal Bovine Serum이 첨가된 -MEM 배양약으로 배양한 조골세포주인 MC3T3E1 세포에 tumor necrosis factor-α (TNF-α), interferon-r (IFN-r) 및 lipopolysacchalide(LPS)등의 단독처리 시 NO와 IL-6의 증가는 확인되지 않았으나 TNF-α/IFN-r 혹은 LPS/IFN-r 등의 처치시 NO 와 IL-6이 유의한 증가를 보였으며, NO발현에 직접 관여하는 inducible nitric oxide synthase (iNOS)와 IL-6 단백질 및 mRNA의 발현을 관찰하였다. 또한 specific p-38 MAP kinase inhibitor인 SB203580의 NO와 IL-6의 생성 억제를 관찰하고 단백질과 mRAN 발현억제를 통해서도 확인함으로써 SB203580은 transcription 단계에서 NO와 IL-6의 생성을 조절하고 있음을 시사하여 주고 있다. TNF-α/IFN-r 혹은 LPS/IFN-r 처치 시 p-38 MAP Kinase의 활성을 관찰하였으나 단독 처치 시 역시 p-38 MAP Kinase의 활성율 확인함으로써 NO 와 IL-6유리를 확인하였으며, 또한 이들의 생성기전중의 하나로 p-38 MAP Kinase 가 transcription 단계에서 관여하고 있음을 확인하였다. Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(116) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytokines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-l osteoblast cultures with combined interferon-y(IFN-r), lipopolysaccharide,(LPS) and tumor necrosis factor-a(TNF-a) induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, IFN-r, LPS, and TNF-a individually induce a non-detectable or small amount of NO and IL-6 in AMC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iI1OS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4fuorophenyi)-2-(4-metylsulfinylphenyl)-5-(4pyridyl)imidazole) (SB203580), were significantly diminished, In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p38 MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in LPS/IFNr- or TNF-a/IFN-r-treated MC3T3E-1 osteoblasts.

Long Intergenic Non-Protein Coding RNA 665 Regulates Viability, Apoptosis, and Autophagy via the MiR-186-5p/MAP4K3 Axis in Hepatocellular Carcinoma

Yong Shan,Ping Li 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.9

Purpose: Long intergenic non-protein coding RNA 665 (LINC00665) plays a vital role in the development of cancer. Its functionin hepatocellular carcinoma (HCC), however, remains largely unknown. Materials and Methods: The expressions of LINC00665, miR-186-5p, and MAP4K3 were determined by qRT-PCR. Cell viabilityand apoptosis were evaluated by MTT and flow cytometry, respectively. Autophagic puncta formation was observed by fluorescencemicroscopy. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and RNA pulldown were performedto identify associations among LINC00665, miR-186-5p, and MAP4K3. Western blot was utilized to examine the expressionsof MAP4K3, Beclin-1, and LC3. Tumor growth was evaluated in a xenograft model. Results: Elevations in LINC00665 were observed in HCC tissues and cells. The overall survival of HCC patients with high levels ofLINC00665 was shorter than those with low levels. In vitro, LINC00665 depletion inhibited viability and induced apoptosis andautophagy. miR-186-5p interacted with LINC00665 and was downregulated in HCC tissues and cells. Upregulation of miR-186-5p inhibited viability and induced apoptosis and autophagy, which were attenuated by upregulation of LINC00665. MAP4K3 wasfound to possess binding sites with miR-186-5p and was upregulated in HCC tissues and cells. MAP4K3 depletion inhibited viabilityand induced apoptosis and autophagy, which were attenuated by miR-186-5p inhibitor. In vivo, miR-186-5p expression wasnegatively correlated with LINC00665 or MAP4K3 in HCC tissues, while LINC00665 was positively correlated with MAP4K3. LINC00665 knockdown suppressed tumor growth. Conclusion: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which mayprovide a new approach for HCC treatment.

MAP를 이용한 축산폐수와 하수의 혼합처리 특성

이순영 ( Soon-young Lee ),원찬희 ( Chan-hee Won ),김명희 ( Ming-ji Jin ),이형원 ( Hyung-won Lee ) 한국환경기술학회 2007 한국환경기술학회지 Vol.8 No.3

본 연구에서는 슬러리 형태의 축산 폐수내 고형물을 분리하기 위해 화학적 응집처리방법을 적용하여 폐수내 부유물질을 최대로 제거한 후, 하수와 다시 혼합하여 MAP공정의 최적처리 조건을 규명하는데 있다. 축산폐수내 고형물을 제거하기 위한 최적 응집조건인 BF02 2mL와 C-210EL(a cationic polymer) 100mL를 축산폐수와 하수를 2:1로 혼합한 폐수 1L에 대해 각각 주입하여 SS의 제거효율이 97.6%인 응집처리수(이하 응집처리수라 함)에 대해서 응집처리수 단독 및 응집처리수와 하수를 혼합하여 MAP 공법을 실시하였다. 응집처리수 단독으로 MAP 처리한 결과, MgO 1M과 H₃PO₄ 0.3M 첨가시 NH₄-N 86%, PO₄-P 99%로 최적 제거율을 나타내었다. 응집처리수를 하수와 2:1로 혼합하여 인을 첨가했을 때와 첨가하지 않았을 때 MgO와 Mg(OH)₂를 각각 첨가하였을 때 비교해 본 결과, 역시 1M MgO와 0.3M H₃PO₄를 첨가했을때 NH₄-N가 87.6%, PO₄-P가 99.2%로 가장 좋은 결과를 얻었다. 응집처리수를 하수와 3:1로 혼합했을때도 역시 1M MgO와 0.3M H₃PO₄에서 첨가했을때 NH₄-N가 87.9%, PO₄-P가 99.8%로 동일한 결과를 나타내었다. 모든 실험에서 Mg(OH)₂의 보다는 MgO가 약간 상향 제거 되는 것으로 나타났다. The main objective of this research was to examine mixing treatment characteristics of pretreatment livestock wastewater and sewage using MAP process. 97.6% of SS removal efficiency was achieved when 2ml BF02(a coagulant) and 100mL C-210EL(a cationic polymer) were added to the mixture(2:1, v/v, 1L) of livestock wastewater and sewage. and then applied MAP process after that pretreatment wastewater and mixed wastewater of pretreatment wastewater and sewage again. The result of MAP treatment on pretreatment wastewater, each of NH₄-N and PO₄-P removal were best in 86% and 99% when MgO 1M and H₃PO₄ 0.3M added. The result of MAP treatment on mixed wastewater of pretreatment wastewater and sewage(2:1, v/v) , each of NH₄-N and PO₄-P removal were best in 87.6% and 99.2% when MgO 1M and H₃PO₄ 0.3M added. The result of MAP treatment on mixed wastewater of pretreatment wastewater and sewage(3:1, v/v) , each of NH4-N and PO₄-P removal were best in 87.9% and 99.8% when MgO 1M and H₃PO₄ 0.3M added. All test is removed more MgO than Mg(OH)₂.

The role of p38 MAP kinase on RANKL regulation in mouse periodontal ligament fibroblasts

김재철,최득철,김영준,Kim, Jae-Cheol,Cui, De-Zhe,Kim, Young-Joon The Korean Academy of Periodontoloy 2007 Journal of Periodontal & Implant Science Vol.37 No.2

Receptor activation of nuclear factor ${\kappa}$ B ligand (RANKL)은 파골세포의 분화와 기능에 중요한 역할을 하는 단백질로 이들 물질의 조절에는 p38 MAP kinase가 관여한다. 그러나 치주인대 섬유모세포에서 RANKL 발현 시 p38 MAP kinase의 역할은 잘 알려져 있지 않다. 이에 이번 연구는 마우스 치주인대 섬유모세포의 $IL-1{\beta}-induced$ RANKL 발현과정에서 p38의 역할을 규명하고자 하여 다음과 같은 결과를 얻었다. 마우스 치주인대 섬유모세포에 $IL-1{\beta}$ (1ng/ml)의 자극은 수용성 RANKL의 합성을 증가시켰다. 수용성 RANKL의 합성은 p38 MAP kinase 억제제인 SB203580에 의해 농도 의존적으로 억제되었으나 다른 MAP kinase 억제제인 SP600125, JNK 억제제와 PD98059, ERK 억제제에 의해서는 수용성 RANKL의 합성이 조절되지 않았다. NF-kB 억제제에 의해서도 수용성 RANKL의 합성이 억제되지 않았다. RANKL 유전자의 발현은 $IL-1{\beta}$로 자극 시에는 대조군에 비해 약 5배의 발현 증가를 보였으나 SB203580으로 전처치 시 $IL-1{\beta}$ (1ng/ml)로 자극시보다 약 1.5배의 감소를 보였다. 그러나 SP600125, PD98059, 및 NF-kB 억제제로 전처치한 경우에는 $IL-1{\beta}$로 자극한 경우와 비슷한 수준을 보였다. $IL-1{\beta}$로 자극 시 RANKL 유전자의 반감기가 90분 이었으나 SB203580로 전처치 후 $IL-1{\beta}$로 자극 시 RANKL 유전자의 반감기는 60분으로 감소하였다. Cycloheximide 전처리 시 SB203580에 의한 RANKL 유전자 발현 억제가 관찰되지 않았다. 단백질 분석결과 p38 MAP kinase의 인산화 활성은 30분까지 증가하였으나 그 이후 감소하여 2시간째에는 그 발현이 미약하였다. SB203580로 전처치 후 $IL-1{\beta}$로 자극 시 p38 MAP kinase의 인산화 활성이 감소하였다. 이상의 결과는 p38 MAP kinase가 RANKL 유전자 조절에 중요한 역할을 담당하고 있음을 시사한다.

DNM3OS Facilitates Ovarian Cancer Progression by Regulating miR-193a-3p/MAP3K3 Axis

Lei He,Guolin He 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.6

Purpose: Long non-coding RNAs (lncRNAs) are essential regulators in the development of ovarian cancer (OC). Nonetheless, thefunction of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in OC remains unclear. This work aimed to investigate thebiological roles and underlying mechanisms of DNM3OS in OC. Materials and Methods: Quantitative real-time polymerase chain reaction was conducted to examine DNM3OS, microRNA(miR)-193a-3p, and mitogen-activated protein kinase 3 (MAP3K3) mRNA expression in OC tissues and cell lines. Kaplan-Meiersurvival analysis was employed to analyze the relationship between DNM3OS expression and the prognosis of OC patients. Cellcounting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell experiments were conducted to monitor cell proliferation, migration,and invasion, respectively. Western blot was applied to examine epithelial-mesenchymal transition associated protein (E-cadherinand N-cadherin) expression. Luciferase reporter gene and RNA immunoprecipitation experiments were performed to confirmthe relationships among DNM3OS, miR-193a-3p, and MAP3K3. Pearson’s correlation analysis was adopted to analyze thecorrelations among DNM3OS, miR-193a-3p, and MAP3K3 mRNA. Results: DNM3OS expression was remarkably increased in OC tissues and cell lines, which was associated with the unfavorableprognosis of the patients. DNM3OS overexpression enhanced OC cell proliferation, migration, and invasion; suppressed E-cadherinprotein expression; and facilitated N-cadherin protein expression, while the transfection of miR-193a-3p mimics had the oppositeeffects. DNM3OS directly interacted with miR-193a-3p, and miR-193a-3p targeted MAP3K3 by directly binding to 3'UTR. DNM3OS could up-regulate the expression of MAP3K3 via repressing miR-193a-3p expression. Conclusion: DNM3OS, as an oncogenic lncRNA, increases the malignancy of OC cells via regulation of an miR-193a-3p/MAP3K3 axis.

HQSAR Study on Imidazo[1,2-b]pyridazine Derivatives as p38 MAP Kinase Antagonists

Bhujbal, Swapnil P.,Keretsu, Seketoulie,Cho, Seung Joo The Basic Science Institute Chosun University 2018 조선자연과학논문집 Vol.11 No.2

p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model ($q^2=0.522$, SDEP=0.479, NOC=5, $r^2=0.703$, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

Interaction of Microtubule-associated Protein 1B Light Chain (MAP1B-LC1) and p53 Represses Transcriptional Activity of p53

김정웅,김소연,정미희,장상민,송기현,김철홍,김여진,최경희 한국통합생물학회 2008 Animal cells and systems Vol.12 No.2

The tumor suppressor and transcription factorp53 is a key modulator of cellular stress responses, and cantrigger apoptosis in many cell types including neurons. Inprotein 1B (MAP1B) light chain interacts with tumorsuppressor p53. MAP1B is one of the major cytoskeletalproteins in the developing nervous system and essential informing axons during elongation. We also demonstrate thatboth p53 and MAP1B-LC1 interact in the nucleus in HEK293 cells. Indeed, we show that the MAP1B-LC1 negativelyregulates p53-dependent transcriptional activity of a reportercontaining the p21 promoter. Consequently, MAP1B lightchain binds with p53 and their interaction leads to thecells. Furthermore, these examinations might be taken intoconsideration when knock-down of MAP1B-LC1 is used asa cancer therapeutic strategy to enhance p53’s apoptoticactivity in chemotherapy.