• 제목/요약/키워드: $21{\alpha}-\

검색결과 2,208건 처리시간 0.031초

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

  • Thu, Vu Thi;Kim, Hyoung Kyu;Long, Le Thanh;Thuy, To Thanh;Huy, Nguyen Quang;Kim, Soon Ha;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권3호
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    • pp.305-314
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    • 2016
  • Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

Effects of the Peroxisome Proliferator Ciprofibrate and Prostaglandin $F_2\alpha$ Combination Treatment on Second Messengers in Cultured Rat Hepatocytes

  • Hong, Jin-Tae;Yun, Yeo-Pyo
    • Archives of Pharmacal Research
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    • 제21권2호
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    • pp.120-127
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    • 1998
  • Peroxisome proliferators induce hepatic peroxisome proliferation and hepatic tumors in rodents. These chemicals increase the expression of the peroxisomal $\beta$-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including eicosanoids. Peroxisome proliferators transiently induce increased cell proliferation in vivo. However, peroxisome proliferators are weakly mitogenic and are not co-mitogenic with epidermal growth factor (EGF) in cultured hepatocytes. Earlier study found that the peroxisome proliferator ciprofibrate is cornitogenic with eicosanoids. In order to study possible mechanisms of the comitogenicity of peroxisome proliferator ciprofibrate and eicosanoids' we hypothesized that the co-mitogenicity may result from synergistic or additive increases of second messengers in mitogenic signal pathways. We therefore examined the effect of the peroxisome proliferator ciprofibrate, prostaglandin $F_2_{\alpha}$($PGF_2{\alpha}$) and the combination of ciprofibrate and $PGF_2{\alpha}$ with or without growth factors on the protein kinase C (PKC) activity, and inositol-1, 4, 5-triphosphate ($IP_{3-}$) and intracellular calcium ($[Ca^{2+}]_i$) concentrations in cultured rat hepatocytes. The combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased particulate PKC activity. The combination of ciprofibrate and $PGF_2{\alpha}$ also significantly increased EGF, transforming growth factor-$\alpha$ ($TGF_2{\alpha}$) and hepatic growth factor (HGF)-induced particulate PKC activity. The combination of ciprofibrate and $PGF_2_\alpha$greatly increased $[Ca^{2+}]_i$. However, the increases of PKC activity and $[Ca^{2+}]_i$ by ciprofibrate and $PGF_2{\alpha}$ alone were much smaller. Neither ciprofibrate or $PGF_2{\alpha}$ alone nor the combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased the formation of $IP_3$. The combination of ciprofibrate and $PGF_2{\alpha}$, however, blocked the inhibitory effect of $TGF-{\beta}$ on particulate PKC activity and formation of $IP_3$ induced by EGF. These results show that co-mitogenicity of the peroxisome proliferator ciprofibrate and eicosanoids may result from the increase in particulate PKC activity and intracellular calcium concentration but not from the formation of $IP_3$.

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Differential Coupling of G$\alpha$q Family of G-protein to Muscarinic $M_1$ Receptor and Neurokinin-2-Receptor

  • Lee, Chang-Ho;Shin, In-Chul;Kang, Ju-Seop;Koh, Hyun-Chul;Ha, Ji-Hee;Min, Chul-Ki
    • Archives of Pharmacal Research
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    • 제21권4호
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    • pp.423-428
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    • 1998
  • The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family $\alpha$ subunits. In order to shed some light on these complex signal processing networks, interactions between G$\alpha$q family of G protein and neurokinin-2 receptor as well as muscarinic M$_{1}$ receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G.alpha.q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of [$^3H$]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of Gaq family of G-protein to muscarinic M$_{1}$ receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G$\alpha$q, G$\alpha$11 and G$\alpha$14 but not G$\alpha$16 and the ability of the muscarinic $M_1$ receptor to activate phospholipase C through G$\alpha$/11 but not G$\alpha$14 and G$\alpha$16 was demonstrated. Clearly G$\alpha$/11 can couple $\M_1$ and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G$\alpha$14 and G$\alpha$16 subunits to these receptors.

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Tissue microarray를 이용한 여러 암에서의 thymosin β4, vascular endothelial growth factor, 및 hypoxia-inducible factor-1α 발현양상 연구 (Analysis of the Expression Patterns of Thymosin β4, Vascular Endothelial Growth Factor, and Hypoxia-Inducible Factor-1α in Various Tumors Using Tissue Microarray)

  • 이보영;이승현;안병권;옥미선;차희재
    • 생명과학회지
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    • 제21권3호
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    • pp.417-423
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    • 2011
  • 사이모신 베타 4와 관련 단백질인 HIF-$1{\alpha}$ 및 VEGF의 발현을 여러 인간 암 조직에서 tissue microarray를 사용하여 조사하였다. 사이모신 베타 4는 골육중, 대장 선암, 식도 편평세포암, 신장 및 방광의 이행세포암, 폐암 및 간암에서 많이 발현되었으며 HIF-$1{\alpha}$은 비강 역위성 유두종, 폐암 및 식도 편평세포암에서 강한 발현을 보였으며 대체로 발현되는 양상이나 위치가 사이모신 베타 4와 일치하는 것으로 관찰되었다. VEGF는 암 조직에서보다 암조직에 분포된 혈관내피에서 강하게 발현되는 양상을 나타내었으며 암세포에서는 사이모신 베타 4나 HIF-$1{\alpha}$에 비해 강하게 발현되지 않았다. 위암, 간 혈관육종, 담낭 선암과 자궁 내막 선암에서 적당 수준의 VEGF 발현이 관찰되었으며 VEGF의 발현 양상 및 위치는 위암, 골육종, 지방종, 폐암, 간암, 담낭 선암, 식도 편평세포암, 대장 및 직장암, 신세포암을 포함하는 특정 암에서 사이모신 베타 4 및 HIF-$1{\alpha}$와 일치하는 것으로 관찰되었다.

금형 주조한 GZ21 합금과 AZ91 합금의 부식특성 비교 (Comparison of Electrochemical Corrosion Properties of Permanent Mold Casting GZ21 Alloy and AZ91 Alloy)

  • 김대한;김병호;박경철;장인기
    • 한국주조공학회지
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    • 제36권2호
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    • pp.60-66
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    • 2016
  • In this study, comparison of corrosion properties of the Mg-1.5Ge-1Zn (GZ21) alloy and Mg-9Al-1Zn (AZ91) alloy were investigated. The studied alloys were fabricated by permanent mold casting method. And the potentiodynamic test, hydrogen evolution test, immersion test and A.C Impedance test were carried out in a 3.5% NaCl solution with pH7.2 at room temperature to measure the corrosion properties. The microstructure of GZ21 alloy was composed of ${\alpha}-Mg$ and $Mg_2Ge$ phases and AZ91 alloy was composed of ${\alpha}-Mg$ and $Mg_{17}Al_{12}$ phases. From the test results, the corrosion property was improved by adding Ge. It seemed that the corrosion mechanism was changed from galvanic corrosion (AZ91) to filiform corrosion (GZ21).

Purification and Characterization of a Major Fibrinolytic Enzyme from Bacillus amyloliquefaciens MJ5-41 Isolated from Meju

  • Jo, Hyeon-Deok;Lee, Hwang-A;Jeong, Seon-Ju;Kim, Jeong-Hwan
    • Journal of Microbiology and Biotechnology
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    • 제21권11호
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    • pp.1166-1173
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    • 2011
  • Meju is a traditional Korean fermented soy product used as a key element for soy sauce and doenjang. Bacilli with antimicrobial activity were isolated from meju prepared by traditional methods at Sunchang county, Jeollabukdo, Korea. Six isolates were identified as Bacillus amyloliquefaciens by recA gene sequencing and RAPD-PCR. One isolate, B. amyloliquefaciens MJ5-41, showed the strongest fibrinolytic activity. A 27 kDa active fibrinolytic enzyme, AprE5-41, was purified from the culture supernatant of MJ5-41 grown on LB by chromatographic methods. The optimum pH and temperature for purified AprE5-41 were 7.0 and $45^{\circ}C$, respectively. AprE5-41 quickly degraded $A{\alpha}$ and $B{\beta}$ chains but not the ${\gamma}$-chain of fibrinogen. AprE5-41 exhibited the highest specificity for N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a known substrate for ${\alpha}$-chymotrypsin, cathepsin G, and subtilisin BPN'. The structural gene, aprE5-41, was cloned by PCR and successfully expressed in B. subtilis.

한우 Lactoferrin이 TNF-$\alpha$와 NO 생성에 미치는 영향 (Effect of Lactoferrin from Korean Native Cattle on the Production of Tumor Necrosis Factor-$\alpha$ and Nitric Oxid)

  • 이수원;양희진;황보식
    • 한국축산식품학회지
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    • 제21권4호
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    • pp.374-382
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    • 2001
  • Lf는 cytokines의 생성 및 면역반응 등의 생체 방어적 기능을 하는 물질로 알려져 있다. 본 연구에서는 Lf과 Lf-h에 의해 macrophage에서 TNF-$\alpha$와 NO 생성에 미치는 효과를 조사하였다. K-Lf 및 K-Lf-h는 단독으로 TNF-$\alpha$의 생성을 증가시켰으며, Lf의 농도에 따라 그 생성량이 증가하였다. LPS와 함께 작용시켰을 경우에는 큰 효과가 없는 것으로 나타났으나, 세포 성장률은 증가시켰다. 그러나 B-Lf, H-Lf, 그리고 이들의 가수분해물들은 단독으로는, RAW264.7 cell을 자극하여 TNF-$\alpha$나 NO의 생성을 증가시키지 못하였다. 또한, K-Lf는 그 자체만으로 TNF-$\alpha$에서 보여준 것처럼 NO생성에 영향을 미치며 농도가 높아짐에 따라 NO 생성을 증가시키는 경향을 보여주었다.

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병원 의료종사자의 환자안전관리 중요성 인식 측정도구 개발 (Development of a Perception of Importance on Patient Safety Management Scale (PI-PSM)for Hospital Employee)

  • 박미정;김인숙;함영림
    • 한국콘텐츠학회논문지
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    • 제13권5호
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    • pp.332-341
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    • 2013
  • 복잡하고 긴박한 상황이 벌어지고 있는 병원 환경에서 환자에게 안전한 돌봄을 제공하기 위해서는 환자안전관리에 대한 병원 의료종사자들의 관심과 그 중요성에 대한 인식이 전제되어야 한다. 이에 본 연구는 병원에서 근무하는 다양한 의료종사자들을 대상으로 그들이 인식하는 환자안전관리 중요성을 측정하기 위한 도구를 개발하고 타당도와 신뢰도를 검정하고자 시도되었다. 환자안전관리 중요성 인식 측정도구는 기초문항 작성, 내용타당도 검정 및 사전조사의 과정을 통해 21문항이 구성되었다. 그리고 280명의 의료종사자를 대상으로 주성분 분석을 이용한 요인분석과 Cronbach's ${\alpha}$ 계수 산출을 통해 도구의 타당도와 신뢰도를 확인받았다. 전체 도구의 설명력은 60.4%였으며, '환자안전관리에 대한 관심(7문항)', '환자안전관리에 대한 자신감(5문항)', '환자안전관리를 위한 의지(5문항)', 그리고 '환자안전관리에 대한 인지(4문항)'의 4개 요인이 추출되었다. 측정도구 21문항의 신뢰계수는 Cronbach's ${\alpha}$=.86이었으며, 4개 요인의 신뢰계수는 .69-.87의 범위를 나타냈다. 추후 다양한 의료 영역에서 안전한 의료 및 간호 제공을 위해, 본 연구에서 개발되고 타당도와 신뢰도가 입증된 환자안전관리 중요성 인식 측정도구가 유용한 측정 지표로서 활용될 수 있기를 기대해 본다.