• 제목/요약/키워드: $S_N1$ mechanism

검색결과 717건 처리시간 0.025초

디엘드린 유도성 소포체 스트레스에서의 parkin과 Bcl-2의 신경보호 효과 (Neuroprotective Effects of Parkin and Bcl-2 against Dieldrin-induced Endoplasmic Reticulum Stress)

  • 서정연;김재성;김도경;전홍성
    • 생명과학회지
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    • 제32권10호
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    • pp.771-777
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    • 2022
  • 파킨슨병에서의 도파민 신경세포의 사멸 원인은 다양하며 별개의 유전적 요소와 환경적 요소들이 관여한다. 드물게 발생하는 유전성 파킨슨병에서 parkin의 돌연변이와 기능 상실은 주로 소포체 스트레스를 통해 중뇌 흑질의 도파민 신경세포를 특이적으로 손상시킨다. 상대적으로 일반적인 특발성 파킨슨병에서는 살충제 노출이 역학적으로 중요하다. 그러나 환경독성물질에의 노출과 유전성 파킨슨병의 연관성에 대해서는 잘 알려진 바가 없다. 본 연구에서는 잘 확립된 중뇌 유래의 도파민 신경세포주인 N27-A를 사용하여 특발성 파킨슨병과 유전성 파킨슨병 사이의 공통된 발병 기작의 증거를 확인하였다. 특발성 파킨슨병을 유발하는 유기염소계 살충제인 디엘드린은 BiP/Grp78, 헴산화효소-1과 같은 소포체 스트레스 반응 표지자를 발현 유도하였고, 특히 parkin 단백질의 발현을 증가시켰다. 디엘드린이 N27-A 세포를 사멸시키는 과정에서 소포체 스트레스 특이적 세포사를 매개하는 Caspase-12의 활성화가 유의미하게 증가하였다. 흥미롭게도 디엘드린에 의한 N27-A 세포의 사멸이 소포체 단백질인 parkin과 Bcl-2의 과발현시 유의미하게 억제되었다. 본 연구 결과, 소포체 스트레스의 누적이 특발성, 유전성 파킨슨병의 공통의 발병 기작일 가능성이 있으며, 몇 가지 소포체 관련 단백질들이 디엘드린에 의한 도파민 신경세포 손상으로부터 보호 효과를 가지는 것으로 보인다.

심혈관계의 중추조절에 대한 Prostaglandin $F_{2{\alpha}}$의 영향 (Effect of Prostaglandin $F_{2{\alpha}}$ on the Central Regulation of Cardiovascular Effect in Conscious Rat)

  • 이상복;김인순;김옥녀;조규철
    • 대한약리학회지
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    • 제18권1호
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    • pp.11-16
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    • 1982
  • This study was carried out in order to clarify whether the cardiovascular effect of prostaglandin(PG) $F_{2{\alpha}}$ might be centrally mediated. In unrestrained conscious rat, $PGF_{2{\alpha}}$ was administered into the lateral ventricle. The mechanism of action was also studied by observing the interaction with several adrenergic antagonists injected subcutaneously, Indomethacin was administered into lateral ventricle to investigate the role of endogenous $PGF_{2{\alpha}}$ on the central regulation of cardiovascular system. The results were as follows: 1) The intraventricular injection of $PGF_{2{\alpha}}$ produced an increase in blood pressure and heart rate. 2) The pretreatment with phenoxybenzamine (2 mg/g, s.c.) inhited pressor, but not heart rate responses to the intraventricular injection of $PGF_{2{\alpha}}$ $(2{\mu}g/kg)$. 3) The pretreatment with propranolol (1 mg/kg, s.c.) inhibited tachycardia, but not pressor responses to the intraventricular injection of $PGF_{2{\alpha}}(2{\mu}g/kg)$. 4) The intraventricular injection of indomethacin $(40{\mu}g/kg)$ could not induce significant changes in blood preesure and heart rate. 5) The result indicates that intraventricular injection of $PGF_{2{\alpha}}$ produces pressor and tachycardia responses in the unanesthetized rat, and it is mediated primarily by centrally increased sympathetic outflow. But the endogenous $PGF_{2{\alpha}}$ synthetized in the brain seems to play minor role in the direct regulation of cardiovascular system.

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A Protein Tyrosine Phosphatase Inhibitor, Pervanadate, Inhibits Angiotensin II-Induced β-Arrestin Cleavage

  • Jang, Sei-Heon;Hwang, Si Ae;Kim, Mijin;Yun, Sung-Hae;Kim, Moon-Sook;Karnik, Sadashiva S.;Lee, ChangWoo
    • Molecules and Cells
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    • 제28권1호
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    • pp.25-30
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    • 2009
  • ${\beta}$-Arrestins turn off G protein-mediated signals and initiate distinct G protein-independent signaling pathways. We previously demonstrated that angiotensin $AT_1$ receptorbound ${\beta}$-arrestin 1 is cleaved after $Phe^{388}$ upon angiotensin II stimulation. The mechanism and signaling pathway of angiotensin II-induced ${\beta}$-arrestin cleavage remain largely unknown. Here, we show that protein Tyr phosphatase activity is involved in the regulation of ${\beta}$-arrestin 1 cleavage. Tagging of green fluorescent protein (GFP) either to the N-terminus or C-terminus of ${\beta}$-arrestin 1 induced conformational changes and the cleavage of ${\beta}$-arrestin 1 without angiotensin $AT_1$ receptor activation. Orthovanadate and molybdate, inhibitors of protein Tyr phosphatase, attenuated the cleavage of C-terminal GFP-tagged ${\beta}$-arrestin 1 in vitro. The inhibitory effects of okadaic acid and pyrophosphate, which are inhibitors of protein Ser/Thr phosphatase, were less than those of protein Tyr phosphatase inhibitors. Cell-permeable pervanadate inhibited angiotensin II-induced cleavage of ${\beta}$-arrestin 1 in COS-1 cells. Our findings suggest that Tyr phosphorylation signaling is involved in the regulation of angiotensin II-induced ${\beta}$-arrestin cleavage.

수질 중 질소와 인 모니터링을 위한 혼합이온교환수지 캡슐의 개발 (Development of Mixed-bed Ion Exchange Resin Capsule for Water Quality Monitoring)

  • 박창진;김동국;옥용식;유경렬;이주영;장용선;양재의
    • Applied Biological Chemistry
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    • 제47권3호
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    • pp.344-350
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    • 2004
  • 본 연구는 혼합이온교환수지 캡슐이 수질 모니터링 도구로 활용가능한지를 평가하기 위해 수행되었다. 이를 위해 수지의 질소$(NH_4\;^+-N,\;NO_3\;^--N)$와 인산$(PO_4\;^{3-}-P)$에 대한 물리적, 화학적 반응 특성을 구명하고, 현장적용시험을 수행하였다. 실험결과 유속이 증가함에 따라 수지의 이온 흡착량은 감소하였으며, 이온 종류에 따른 흡착량은 $NO_3\;^--N\;>\;NH_4\;^+-N\;>\;PO_4\;^{3-}-P$ 순으로 나타나 수지의 흡착 선택성과 일치하였다. 온도와 시간에 따른 이온의 농도 변화를 일차반응속도모델에 적용하였을 때, 반응비상수$({\kappa})$는 반응온도가 증가함에 따라 증가하였고, 이온의 농도가 증가함에 따라 증가하였다. 온도가 증가함에 따라 ${\Delta}H^{o\ddag}$값과 ${\Delta}G^{o\ddag}$값은 증가하였으나, $E_a$값과 ${\Delta}S^{o\ddag}$값은 감소하여 열역학 이론과 일치하였다. $E_a$$155.38{\sim}682.89\;kJ{\cdot}mol^{-1},\;{\Delta}H^{o\ddag}$$153.03{\sim}680.54\;kJ{\cdot}mol^{-1},\;{\Delta}S^{o\ddag}$$525.02{\sim}610.99\;J{\cdot}mol^{-1},\;K^{-1}\;{\Delta}G^{o\ddag}$$525.02{\sim}610.99\;J{\cdot}mol^{-1}$의 범위를 나타냈다. 현장적용시험에서 삽입시간과 수지흡착량의 관계는 Langmuir 형태를 따랐으며, 질소는 24시간 경과 후, 인산은 8시간 후에 의사평형에 도달하였다. 따라서 현장에서의 최대 삽입시간은 인산의 평형 도달시간과 하천 내 인산 농도에 의해 결정될 것으로 판단된다. 이상의 결과를 통해 이온교환수지를 수질 중 질소와 인의 모니터링 도구로 활용할 수 있을 것으로 판단되며, 실제 현장에 활용하기 위해서는 온도, 유속, 삽입시간 등의 인자와 하천수 내 이온조성과의 상관관계에 대한 규명과 경험상수의 도출이 필요할 것으로 판단된다.

하이드라진 방법에 의한 ZnO 미분말의 합성 및 에탄올 감응성 (Preparation of ZnO Powders by Hydrazine Method and Its Sensitivity to C2H5OH)

  • 김선중;이종흔
    • 한국재료학회지
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    • 제18권11호
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    • pp.628-633
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    • 2008
  • ZnO nanopowders were synthesized by the sol-gel method using hydrazine reduction, and their gas responses to 6 gases (200 ppm of $C_2H_5OH$, $CH_3COCH_3$, $H_2$, $C_3H_8$, 100 ppm of CO, and 5 ppm of $NO_2$) were measured at $300\;{\sim}\;400^{\circ}C$. The prepared ZnO nanopowders showed high gas responses to $C_2H_5OH$ and $CH_3COCH_3$ at $400^{\circ}C$. The sensing materials prepared at the compositions of [$ZnCl_2$]:[$N_2H_4$]:[NaOH] = 1:1:1 and 1:2:2 showed particularly high gas responses ($S\;=\;R_a/R_g,\;R_a$ : resistance in air, $R_g$ : resistance in gas) to 200 ppm of $C_2H_5OH$($S\;=\;102.8{\sim}160.7$) and 200 ppm of $CH_3COCH_3$($S\;= 72.6{\sim}166.2$), while they showed low gas responses to $H_2$, $C_3H_8$, CO, and $NO_2$. The reason for high sensitivity to these 2 gases was discussed in relation to the reaction mechanism, oxidation state, surface area, and particle morphology of the sensing materials.

Basic characteristics of metal-ferroelectric-insulator-semiconductor structure using a high-k PrOx insulator layer

  • Noda, Minoru;Kodama, Kazushi;Kitai, Satoshi;Takahashi, Mitsue;Kanashima, Takeshi;Okuyama, Masanori
    • E2M - 전기 전자와 첨단 소재
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    • 제16권9호
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    • pp.64.1-64
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    • 2003
  • A metal-ferroelectric [SrBi$_2$Ta$_2$O$\_$9/ (SBT)-high-k-insulator(PrOx)-semiconductor(Si) structure has been fabricated and evaluated as a key part of metal-ferroelectric-insulator-semiconductor-field-effect-transistor MFIS-FET memory, aiming to improve the memory retention characteristics by increasing the dielectric constant in the insulator layer and suppressing the depolarization field in the SBT layer. A 20-nm PrOx film grown on Si(100) showed both a high of about 12 and a low leakage current density of less than 1${\times}$ 10e-8 A/$\textrm{cm}^2$ at 105 MV/cm. A 400-nm SBT film prepared on PrOx/Si shows a preferentially oriented (105) crystalline structure, grain size of about 130 nm and subface roughness of 3.2 nm. A capacitance-voltage hysteresis is confirmed on the Pt/SBT/PrOx/Si diode with a memory window of 0.3V at a sweep voltage width of 12 V. The memory retention time was about 1 104s, comparable to the conventional Pt/SBT/SiO$\_$x/N$\_$y/(SiO$\_$N/)/Si. The gradual change of the capacitance indicates that some memory degradation mechanism is different from that in the Pt/SBT/SiON/Si structure.

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의과대학생은 시험을 준비하기 위해 어떻게 공부하는가: 평가 전 인지 및 메타인지 활동 (How Do Medical Students Prepare for Examinations: Pre-assessment Cognitive and Meta-cognitive Activities)

  • 윤소정;이상엽;임선주
    • 의학교육논단
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    • 제21권1호
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    • pp.51-58
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    • 2019
  • Although 'assessment for learning' rather than 'assessment of learning' has been emphasized recently, student learning before examinations is still unclear. The purpose of this study was to investigate pre-assessment learning activities (PALA) and to find mechanism factors (MF) that influence those activities. Moreover, we compared the PALA and MF of written exams with those of the clinical performance examination/objective structured clinical examination (CPX/OSCE) in third-year (N=121) and fourth-year (N=108) medical students. Through literature review and discussion, questionnaires with a 5-point Likert scale were developed to measure PALA and MF. PALA had the constructs of cognitive and meta-cognitive activities, and MF had sub-components of personal, interpersonal, and environmental factors. Cronbach's ${\alpha}$ coefficient was used to calculate survey reliability, while the Pearson correlation coefficient and multiple regression analysis were used to investigate the influence of MF on PALA. A paired t-test was applied to compare the PALA and MF of written exams with those of CPX/OSCE in third and fourth year students. The Pearson correlation coefficients between PALA and MF were 0.479 for written exams and 0.508 for CPX/OSCE. MF explained 24.1% of the PALA in written exams and 25.9% of PALA in CPX/OSCE. Both PALA and MF showed significant differences between written exams and CPX/OSCE in third-year students, whereas those in fourth-year students showed no differences. Educators need to consider MFs that influence the PALA to encourage 'assessment for learning'.

Ginseng extract and ginsenosides improve neurological function and promote antioxidant effects in rats with spinal cord injury: A meta-analysis and systematic review

  • Sng, Kim Sia;Li, Gan;Zhou, Long-yun;Song, Yong-jia;Chen, Xu-qing;Wang, Yong-jun;Yao, Min;Cui, Xue-jun
    • Journal of Ginseng Research
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    • 제46권1호
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    • pp.11-22
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    • 2022
  • Spinal cord injury (SCI) is defined as damage to the spinal cord that temporarily or permanently changes its function. There is no definite treatment established for neurological complete injury patients. This study investigated the effect of ginseng extract and ginsenosides on neurological recovery and antioxidant efficacies in rat models following SCI and explore the appropriate dosage. Searches were done on PubMed, Embase, and Chinese databases, and animal studies matches the inclusion criteria were selected. Pair-wise meta-analysis and subgroup analysis were performed. Ten studies were included, and the overall methodological qualities were low quality. The result showed ginseng extract and ginsenosides significantly improve neurological function, through the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale (pooled MD = 4.40; 95% CI = 3.92 to 4.88; p < 0.00001), significantly decrease malondialdehyde (MDA) (n = 290; pooled MD = -2.19; 95% CI = -3.16 to 1.22; p < 0.0001) and increase superoxide dismutase (SOD) levels (n = 290; pooled MD = 2.14; 95% CI = 1.45 to 2.83; p < 0.00001). Both low (<25 mg/kg) and high dosage (25 mg/kg) showed significant improvement in the motor function recovery in SCI rats. Collectively, this review suggests ginseng extract and ginsenosides has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials and applications.

산화망간-이산화티탄계의 결함구조 및 전기전도메카니즘 (Defect Structure and Electrical Conduction Mechanism of Manganese Oxide-Titanium Dioxide)

  • 김규홍;최재시
    • 대한화학회지
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    • 제26권3호
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    • pp.128-134
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    • 1982
  • 0.40, 0.80 및 1.60 mol %의 산화망간을 함유한 이산화티탄의 전기전도도를 $10^{-8}\;to\;10^{-1}$ atm의 산소분압하에서 100 ~ 400$^{\circ}$C 및 1100 ~ 1300$^{\circ}$C의 온도에서 측정하였다. 일정한 산소분압하에서 측정된 전기전도도 값을 온도의 역수에 대하여 도시한 결과 저온 및 고온 영역에서 직선관계를 나타내었으며 활성화에너지는 각각 0.18 및 3.70eV이다. 전기전도도의 산소분압 의존성은 저온영역에서 -1/6이며 고온 영역에서 -1/4이다. 저온 영역과 고온영역에서의 결함구조가 각각(Vo-2e') 및 $Ti^3$임을 밝혔으며 전기전도 메카니즘과 가능한 전도띠 모델이 제안되었다.

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Vascular Endothelial Growth Factor May Be Involved in the Behavioral Changes of Progeny Rats after Exposure to Ceftriaxone Sodium during Pregnancy

  • Yang, Xin;Tang, Ting;Li, Mengchun;Chen, Jie;Li, Tingyu;Dai, Ying;Cheng, Qian
    • Journal of Microbiology and Biotechnology
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    • 제32권6호
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    • pp.699-708
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    • 2022
  • Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring. The antibiotic group offspring showed lower sociability and spatial learning and memory than control. To determine the role of the gut microbiota and their metabolites in the changes in offspring behavior, fecal samples of 6-week-old offspring rats were sequenced. The composition of dominant gut microbial taxa differed between the control and antibiotic groups. KEGG pathway analysis showed that S24-7 exerted its effects through the metabolic pathways including mineral absorption, protein digestion and absorption, Valine, leucine, and isoleucine biosynthesis. Correlation analysis showed that S24-7 abundance was negatively correlated with the level of VEGF, and metabolites associated with S24-7-including 3-aminobutanoic acid, dacarbazine, L-leucine, 3-ketosphinganine, 1-methylnicotinamide, and N-acetyl-L-glutamate-were also significantly correlated with VEGF levels. The findings suggest that antibiotic exposure during pregnancy, specifically ceftriaxone sodium, will adversely affects the behavior of offspring rats due to the imbalance of gut microbiota, especially S24-7, via VEGF and various metabolic pathways.