• 제목/요약/키워드: $S1P_2$

검색결과 24,918건 처리시간 0.049초

Pro-Inflammatory Role of S1P3 in Macrophages

  • Heo, Jae-Yeong;Im, Dong-Soon
    • Biomolecules & Therapeutics
    • /
    • 제27권4호
    • /
    • pp.373-380
    • /
    • 2019
  • Sphingosine kinase 1 and its product, sphingosine 1-phosphate (S1P), as well as their receptors, have been implicated in inflammatory responses. The functions of receptors $S1P_1$ and $S1P_2$ on cell motility have been investigated. However, the function of $S1P_3$ has been poorly investigated. In this study, the roles of $S1P_3$ on inflammatory response were investigated in primary peritoneal macrophages. $S1P_3$ receptor was induced along with sphingosine kinase 1 by stimulation of lipopolysaccharide (LPS). LPS treatment induced inflammatory genes, such iNOS, COX-2, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. TY52156, an antagonist of $S1P_3$ suppressed the induction of inflammatory genes in a concentration dependent manner. Suppression of iNOS and COX-2 induction was further confirmed by western blotting and NO measurement. Suppression of $IL-1{\beta}$ induction was also confirmed by western blotting and ELISA. Caspase 1, which is responsible for $IL-1{\beta}$ production, was similarly induced by LPS and suppressed by TY52156. Therefore, we have shown $S1P_3$ induction in the inflammatory conditions and its pro-inflammatory roles. Targeting $S1P_3$ might be a strategy for regulating inflammatory diseases.

S1P1 Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia

  • Gaire, Bhakta Prasad;Bae, Young Joo;Choi, Ji Woong
    • Biomolecules & Therapeutics
    • /
    • 제27권6호
    • /
    • pp.522-529
    • /
    • 2019
  • M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

Synthesis of Nucleophilic Adducts of Thiols (Ⅰ). Addition of Cysteine to $\beta$-Nitrostyrene Derivatives

  • Kim, Tae-Rin;Choi, Sung-Yong
    • Bulletin of the Korean Chemical Society
    • /
    • 제2권4호
    • /
    • pp.125-129
    • /
    • 1981
  • The addition reactions of cysteine without blocking amino and carboxyl groups to substituted and unsubstituted ${\beta}$-nitro-styrene derivatives were investigated. ${\beta}$-Nitrostyrene(1a), p-methyl-${\beta}$-nitrostyrene(1b), 3,4,5-trimethoxy-$[\beta}$ -nitrostyrene(1c), $[\varpi}$-3,4-methylenedioxy-${\beta}$ -nitrostyrene(1d), o-, m- and p-chloro-${\beta}$ -nitrostyrene (1e, 1f, 1g) and o-, m- and p-methoxy-${\beta}$-nitrostyrene (1h, 1i, 1j) easily undergo addition reactions with cysteine to form S-(2-nitro-1-phenylethyl)-L-cysteine(3a), S-[2-nitro-1-(p-methyl)phenyl-ethyl]-L-cysteine(3b), S-[2-nitro-1-(3',4',5'-trimethoxy) phenylethyl]-L-cysteine(3c), S-[2-nitro-1-($[\vatpi}$ -3',4'-methylenedioxy)phenylethyl]-L-cysteine(3d), S-[2-nitro-1-(o-chloro)phenylethyl]-L-cysteine(3e), S-[2-nitro-1-(m-chloro)-phenylethyl]-L-cysteine(3f), S-[2-nitro-1-(p-chloro)phenylethyl]-L-cysteine(3g), S-[2-nitro-1-(o-methoxy)phenylethyl]-L-cysteine(3h), S-[2-nitro-1-(m-methoxy)phenylethyl]-L-cysteine(3i) and S-[2-nitro-1-(p-methoxy)phenylethyl]-L-cysteine(3j), respectively. The structure of adducts were confirmed by means of UV-spectrum, IR-spectrum, molecular weight measurement and elemental analysis. The various factors effecting the yield of cysteine adducts to ${\beta}$-nitrostyrene derivatives were also studied.

독일어의 신체부위 "손" 관련 관용구의 결합가 연구 (Zur Valenz deutscher verbaler Somatismen mit der Komponente ${\lceil}hand{\rfloor}$)

  • 김수남
    • 한국독어학회지:독어학
    • /
    • 제4집
    • /
    • pp.1-27
    • /
    • 2001
  • 이 글의 목적은 독일어 신체어휘 관련 관용구들 가운데 ${\lceil}$Duden Band 11${\rfloor}$에 수록된 108개의 $\lceil$$\rfloor$ 관련 관용구를 대상으로 이들의 형태$\cdot$통사구조를 파악하고, 그들을 모형화하는 것이다. 우리는 연구 대상을 문장에서 결합가 보유어로서 술어의 기능을 하는 관용구에 한정했다. 우리는 $\lceil$$\rfloor$ 관련 관용구를 보충어의 수와 형태에 따라 크게 세 가지 부류, 즉 1가, 2가, 3가의 관용구로 구분하였다 보충어의 형태는 명사구(Sn, Sd, Sa)와 전치사구(pS)에 한정했으며 문장형태의 보충어, 예를 들어 부문장(NS)과 부정사문(Inf) 형태는 고려하지 않았다. 이들이 보충어로 간주될 수 있는지의 여부는 아직 더 많은 연구를 필요로 하기 때문에 다음 과제로 남겨두었다. 일차적으로 외적 결합가($\"{a}u{\beta}ere\;Valenz)$에 따라, 이차적으로는 내적 결합가(innere Valenz)에 따라 108개의 $\lceil$$\rfloor$ 관련 관용구를 분석한 결과 우리는 다음과 같은 형태$\cdot$통사적 문형을 얻을 수 있었다. $\cdot$ 1가 동사 관용구: 1) PL-Sn : (1) PL[VPL - Sa] - Sn (2) PL(VPL - pS) - Sn (3) PL[VPL - Sa - pS] - Sn (4) PL[VPL - pS - pS] - Sn Sondergruppen: PL[VPL - Sa - Inf] - Sn PL[VPL - pS - Inf] - Sn 2) PL - Sd: (1) PL[VPL - Sn] - Sd (2) PL[VPL - Sn(es) - pS] - Sd $\cdot$ 2가 동사 관용구1) PL - Sn - Sd: (1) PL[VPL - Sa] - Sn - Sd (2) PL[VPL - pS] - Sn - Sd (3) PL[VPL - Sa - pS) - Sn - Sd 2) PL - Sn - pS: (1) PL[VPL - Sa] - Sn - pS (2) PL[VPL - pS] - Sn - pS (3) PL(VPL - Sa - pS) - Sn - pS 3) PL[VPL - pS) - Sn -Sa $\cdot$ 3가 동사 관용구: (1) PL[VPL - pS] - Sn - Sd - Sa (2) PL[VPL - pS] - Sn - Sa - pS (3) PL[VPL - Sa] - Sn - Sd - pS 이러한 분류가 보여주듯이, 독일어에는 1가, 2가, 3가의 관용구가 있으며, 구조 외적으로 동일한 통사적 결합가를 갖는다 하더라도 구조 내적 성분구조가 다르다는 것을 알 수 있다. 우리는 이 글이 외국어로서의 독일어를 배우는 이들에게 독일어의 관용구를 보다 올바르게 이해할 수 있는 방법론적인 토대를 제공함은 물론, (관용어) 사전에서 외국인 학습자를 고려하여 관용구를 알기 쉽게 기술하는 데 도움을 줄 수 있기를 바란다.

  • PDF

출아효모에서 xylitol dehydrogenase (XYL2)의 최적 생산을 위한 발현 시스템 구축 (Expression System for Optimal Production of Xylitol Dehydrogenase (XYL2) in Saccharomyces cerevisiae)

  • 정회명;김연희
    • 생명과학회지
    • /
    • 제27권12호
    • /
    • pp.1403-1409
    • /
    • 2017
  • 본 연구에서는 lignocellulosic biomass (xylose)의 부가가치를 높이고 효율적인 활용을 위해 xylitol dehydrogenase를 Saccharomyces cerevisiae 숙주세포에서 분비 생산하고자 하였다. 먼저 S. cerevisiae와 Pichia stipitis유래 XYL2 유전자(S.XYL2 and P.XYL2 gene)의 발현 시스템을 구축하기 위하여 GAL10 promoter와 ADH1 promoter 하류에 각각 mating factor ${\alpha}$ ($MF{\alpha}$) signal sequence와 XYL2유전자를 가진 $pGMF{\alpha}-S.XYL2$, $pGMF{\alpha}-P.XYL2$, $pAMF{\alpha}-S.XYL2$$pAMF{\alpha}-P.XYL2$ plasmid를 구축하였다. 각각의 plasmid는 S. cerevisiae $SEY2102{\Delta}trp1$ 균주에 형질전환되었고, 생산된 xylitol dehydrogenase의 활성을 조사해 본 결과, GAL10 promoter가 ADH1 promoter보다 XYL2유전자의 발현에 더욱 적합함을 확인 할 수 있었다. 또한 P. stipitis 유래의 xylitol dehydrogenase 효소 활성이 S. cerevisiae 유래의 효소 활성보다 2배 이상 더 높았으며, 활성의 증가를 위해 두 유전자 모두 cofactor로 $NAD^+$에 의존한다는 것을 확인하였다. 재조합 유전자가 가지는 분비서열에 의해 $SEY2102{\Delta}trp1/pGMF{\alpha}-P.XYL2$ 균주에서 xylitol dehydrogenase의 약 77%는 periplasmic space로 분비 발현되었음을 알 수 있었다. 또한 재조합 xylitol dehydrogenase의 효율적인 생산을 위해 탄소원의 영향을 조사해본 결과, glucose 단독보다 glucose와 xylose를 혼합 배양한 경우에서 효소활성이 최대 41% 정도 증가되었음을 확인 할 수 있었다. 본 연구에서 최적화한 발현 시스템 및 배양 조건은 xylose 뿐만 아니라 다양한 biomass를 이용한 유용물질 생산을 위한 관련 단백질의 발현 분비시스템 구축 및 대량생산에도 응용될 수 있을 것이라 생각된다.

Sphingosine-1-phosphate에 의한 중간엽 줄기세포의 이동과 평활근세포로의 분화 (Sphingosine-1-Phosphate-Induced Migration and Differentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells)

  • 송해영;신상훈;김민영;김재호
    • 생명과학회지
    • /
    • 제21권2호
    • /
    • pp.183-193
    • /
    • 2011
  • 중간엽 줄기세포의 이동과 분화는 손상된 조직의 재생을 위해 필수적이다. Sphingosine-1-phosphate (S1P)는 세포성장, 생존, 분화, 이동성 등 여러 가지 생명현상에 중요한 역할을 하는 생리활성 지질이다. 본 연구에서는 인체 골수유래 중간엽 줄기세포의 이동과 세포분화에 대한 S1P의 영향을 조사하였다. S1P는 중간엽 줄기세포의 이동을 증가시켰으며 pertussis toxin의 전처리는 S1P에 의한 세포이동을 억제하였다. 본 결과는 S1P에 의한 세포 이동과정에 Gi에 연결된 수용체가 관여함을 제시한다. $S1P_1$$S1P_3$ 수용체에 대한 길항제인 VPC23019의 전처리나 siRNA를 이용한 $S1P_1$ 수용체의 발현억제는 S1P에 의한 세포 내 칼슘 증가와 중간엽 줄기세포의 이동을 저해 하였다. 또한, S1P의 처리는 중간엽 줄기세포에서 평활근세포의 표지유전자인 $\alpha$-smooth muscle actin ($\alpha$-SMA)의 발현을 증가시켰으며 VPC23019의 전처리는 S1P에 의한 $\alpha$-SMA의 발현증가를 저해하였다. S1P는 중간엽 줄기세포에서 p38 mitogen-activated protein kinase (p38 MAPK)의 인산화를 촉진하였으며 p38 MAPK의 저해제인 SB202190의 전처리 또는 p38 MAPK의 dominant negative mutant의 과발현은 S1P에 의한 중간엽 줄기세포의 이동 $\alpha$-SMA 발현증가를 억제하였다. 본 연구결과는 S1P가 $S1P_1$-p38 MAPK 신호전달기전을 통해 중간엽 줄기세포의 이동과 평활근세포로의 분화를 촉진함으로써 중간엽 줄기세포를 이용한 조직재생에의 활용 가능성을 제시한다.

Synthesis of Nucleophilic Adducts of Thiols (Ⅳ). Addition of Glutathione to $\beta$-Nitrostyrene Derivatives

  • Kim, Tae-Rin;Choi, Sung-Yong;Choi, Won-Sik
    • Bulletin of the Korean Chemical Society
    • /
    • 제4권2호
    • /
    • pp.92-95
    • /
    • 1983
  • The addition products of glutathione to ${\beta}$ -nitrostyrene derivatives were synthesized. ${\beta}$ -Nitrostyrene (1a), p-methyl-${\beta}$-nitrostyrene (1b), 3,4,5-trimethoxy-${\beta}$-nitrostyrene (1c), o-, m- and p-chloro-${\beta}$-nitrostyrene (1e, 1f, 1g) and o-, m- and p-methoxy-${\beta}$-nitrostyrene (1h, 1i, 1j) undergo addition reactions with glutathione to form S-(2-nitro-1-phenylethyl)-L-glutathione (5a), S-[2-nitro-1-(p-methyl)phenylethyl]-L-glutatione (5b), S-[2-nitro-1-(3', 4', 5'-trimethoxy)phenylethyl]-L-glutathione (5c), S-[2-nitro-1-(o-chloro)phenylethyl]-L-glutathione (5e), S-[2-nitro-1-(m-choro)phenylethyl]-L-glutathione (5f), S-[2-nitro-1-(p-chloro)phenylethyl]-L-glutathione (5g), S-[2-nitro-x-(o-methoxy)-phenylethyl]-L-glutathion e(5h), S-[2-nitro-x-(m-methoxy)phenylethyl]-L-glutathion e (5i), and S-[2-nitro-1-(p-methoxy)phenylethy])-L-glutathione (5j), respectively. The structure of adducts were identified by UV and IR-spectra, molecular weight measurement, and elemental analysis.

A NEW CHARACTERIZATION OF ALTERNATING AND SYMMETRIC GROUPS

  • ALAVI S. H.;DANESHKHAW A.
    • Journal of applied mathematics & informatics
    • /
    • 제17권1_2_3호
    • /
    • pp.245-258
    • /
    • 2005
  • In this paper we prove that the alternating groups A_n, for n = p, p+1, p+2 and symmetric groups $S_n$, for n = p, p+1, where p$\ge$3 is a prime number, can be uniquely determined by their order components. As one of the important consequence of this characterization we show that the simple groups An, where n = p, p+1, P+2 and p$\ge$3 is prime, satisfy in Thompson's conjecture and Shi's conjecture.

대구.경북지역 일부 양호교사의 업무수행에 미치는 요인분석 (An Analytic Study on factors Affecting the School Nurse's Activities in Daegu City and Kyungpook Province)

  • 곽오계
    • 지역사회간호학회지
    • /
    • 제1권1호
    • /
    • pp.503-517
    • /
    • 1989
  • This study is to analyze factors affecting the school nurse's activities. The survey was undertaken during Sept. 1-Nov. 30, 1986. The subjects were 137 school nurses from elementary, junior-high, and senior-high schools in Daegu City and Kyungppk Province. The results are as follows: 1. Correlational findings between school nurse's self-confidence and their general characteristics 1) Program Planning & Evaluation: Health Experinece(r=-0.1803, p<0.05) Salary Step(r=-0.1741, p<0.05) 2) Clinic Management: Salary STep(r=-0.2580, p<0.01) 3) Health Education: Salary Step(r=-0.1929, p<0.05) 4) Management of School Environment: Salary Step(r=-0.2501, p<.05) 5) Health Care Services: Health Experience(r=0.1901, p<0.05) Salary Step(r=-0.2424, p<0.05) 2. The degrees of school nurse's self-confidence(high: 4 point, low: 1 point) 1) Clinic Management: 2.92 2) Health Education: 2.86. 3) Program Planning & Evaluation: 2.74 4) Health Care Services: 2.73 5) Management of School Environment: 2.67 6) Operating of School Health Organization: 2.42 3. Significances to self-confidence on school nurse's activities 1) Program Planning as Evaluation: Expending Times for Health Care Services (r=-0.2262, p<0.05) Expending Times for Health Education (r=0.2943, p<0.05) Size of Clinic(r=0.2163, p<0.05) Location of Clinic(t=2.43, gH0.047) Use of Clinic(t=2.06, p<0.007) 2) Clinic Management: Location of Clinic (t=3.36, p<0.010) 3) Health Education: Purchase of Medicine(r=-0.1736, p<0.05) No, of Classes (r=-0.1794, p<0.05) (4) Management of School Environment: School Health Budget(r=0.1731, p<0.05) Home Message(r=0.1805, p<0.05) Location of Clinic(t=4.46, p<0.0001) 5) Operating of School Health Organization: School Health Budget(r=0.1878, p<0.05) Use of Clinic(t:1.90, p<0.018) 6) Health Care Services: School Health Budget(r=1.90, p<0.018) Expending Times for Health Education(r=0.2577, p<0.05) Size of Clinic(r=0.4336, p<0.001) Location of Clinic(t:5.10, p<0.001)

  • PDF

MONOTONICITY PROPERTIES OF THE GENERALIZED STRUVE FUNCTIONS

  • Ali, Rosihan M.;Mondal, Saiful R.;Nisar, Kottakkaran S.
    • 대한수학회지
    • /
    • 제54권2호
    • /
    • pp.575-598
    • /
    • 2017
  • This paper introduces and studies a generalization of the classical Struve function of order p given by $$_aS_{p,c}(x):=\sum\limits_{k=0}^{\infty}\frac{(-c)^k}{{\Gamma}(ak+p+\frac{3}{2}){\Gamma}(k+\frac{3}{2})}(\frac{x}{2})^{2k+p+1}$$. Representation formulae are derived for $_aS_{p,c}$. Further the function $_aS_{p,c}$ is shown to be a solution of an (a + 1)-order differential equation. Monotonicity and log-convexity properties for the generalized Struve function $_aS_{p,c}$ are investigated, particulary for the case c = -1. As a consequence, $Tur{\acute{a}}n$-type inequalities are established. For a = 2 and c = -1, dominant and subordinant functions are obtained for the Struve function $_2S_{p,-1}$.