• Reproductive and Developmental Biology
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• 제35권3호
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• pp.221-225
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• 2011

This study was undertaken to evaluate the relationship between in vitro maturation and plasminogen activators (PAs) activity on porcine cumulus-oocytes complexes (COCs) exposed to oxidative stress. When COCs were cultured in maturation medium with hydrogen peroxide ($H_2O_2$), the proportion of the germinal vesicle breakdown (GVBD) and oocytes maturation were decrease with addition of $H_2O_2$, and were significantly (p<0.05) lower in medium with 0.1 mM $H_2O_2$ than control group. Also, the rate of degenerated oocytes was increased in as $H_2O_2$ concentration in eased. When COCs were cultured for 48 h, three plasminogen-dependent lytic bands were observed: tissue-type PA (tPA); urokinase-type PA (uPA); and tPA-PA inhibitor (tPA-PAI). PA activity was quantified using SDS-PAGE and zymography. When $H_2O_2$ concentration was increased, tPA and tPA-PAI activities also increased in porcine oocytes cultured for 48 h, but not uPA. In other experiment, embryos were divided into three groups and cultured in (1) control medium, (2) control medium with 1.0 mM $H_2O_2$ and (3) control medium with 1.0 mM $H_2O_2$ along with catalase in concentrations of 0.01, 0.1, and 1.0 mg/ml, respectively. $H_2O_2$ decreased the rate of GVBD and maturation in porcine COCs but catalase revealed protective activity, against oxidative stress caused by $H_2O_2$. In this experiment, tPA and tPA-PAI activities were higher in media with 1.0 mM $H_2O_2$ alone. Increasing concentration of catalase decreased tPA and tPA-PAI activities in porcine oocytes. These results indicate that the exposure of porcine follicular oocytes to ROS inhibits oocytes maturation to metaphase-II stage and increase the oocytes degeneration. Also, we speculated that increased ROS level may trigger tPA and tPA-PAI activities in porcine oocytes matured in vitro.

• Biomolecules & Therapeutics
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• 제11권4호
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• pp.205-213
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• 2003

Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

• 한국동물생명공학회지
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• 제34권3호
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• pp.240-246
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• 2019

The aim of this study was to investigate effect of heat stress on expression levels of plasminogen activators (PAs) related mRNAs and proteins, and changes of PAs activity in porcine endometrial explants. The endometrial explants (200 ± 50 mg) were isolated from middle part of uterine horn at follicular phase (Day 19-21) and were pre-incubated in serum-free culture medium at 38.5℃ in 5% CO₂ for 18 h. Then, the tissues were transferred into fresh medium and were cultured at different temperature (38.5, 39.5, 40.5 or 41.5℃) for 24 h. The expression level of urokinase-type PA (uPA), type-1 PA inhibitor (PAI-1), type-2 PAI (PAI-2), and heat shock protein-90 (HSP-90) mRNA were analysis by reverse-transcription PCR and proteins were measured by western blotting. The supernatant were used for measurement of PAs activity. In results, mRNA and protein levels of HSP-90 was higher in 41.5℃ treatment groups than other treatment groups (p < 0.05). The expression of uPA, PAI-1, and PAI-2 mRNA were slightly increased by heat stress, however, there were no significant difference. Heat stress condition suppressed expression of active uPA and PAI-2 proteins (p < 0.05), whereas PAI-1 protein was increased (p < 0.01). Although PAI-1 protein was increased and active uPA was decreased, PAs activity was greatly enhanced by exposure of heat stress (p < 0.05). These results suggest that heat stress condition could change intrauterine microenvironment through regulation of PAs activity and other factors regarding with activation of PAs might be regulate by heat stress. Therefore, more studies regarding with regulatory mechanism of PAs activation are needed.

• BMB Reports
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• 제47권4호
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• pp.227-232
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• 2014

Histone deacetylase-3 (HDAC3) is involved in cellular proliferation, apoptosis and transcriptional repression. However, the role of HDAC3 in angiogenesis remains unknown. HDAC3 negatively regulated the expression of angiogenic factors, such as VEGF and plasminogen activator inhibitor-1 (PAI-1). HDAC3 showed binding to promoter sequences of PAI-1. HDAC3 activity was necessary for the expression regulation of PAI-1 by HDAC3. VEGF decreased the expression of HDAC3, and the down-regulation of HDAC3 enhanced endothelial cell tube formation. HDAC3 negatively regulated tumor-induced angiogenic potential. We show the novel role of HDAC3 as a negative regulator of angiogenesis.

• Journal of Microbiology
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• 제41권4호
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• pp.335-339
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• 2003

Many genetic variants of ${\alpha}_1$-antitrypsin have been associated with early onset emphysema and liver cirrhosis. However, the detailed structural basis of pathogenic ${\alpha}_1$-antitrypsin molecules is rarely known. Here we found that a recombinant $M_{malton}$ variant (Phe52-deleted) lost inhibitory activity by spontaneous conformational conversion into a more stable, inactive form under physiological conditions. Biochemical and spectroscopic data suggested that the variant converts into a reactive center loop-inserted conformation, resembling the latent form of plasminogen activator inhibitor-1.

• BMB Reports
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• 제53권4호
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• pp.240-240
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• 2020

• Korean Journal of Radiology
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• 제20권5호
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• pp.739-748
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• 2019

For recanalization of emergent large vessel occlusions (ELVOs), endovascular therapy (EVT) using newer devices, such as a stent retriever and large-bore catheter, has shown better patient outcomes compared with intravenous recombinant tissue plasminogen activator only. Intracranial atherosclerotic stenosis (ICAS) is a major cause of acute ischemic stroke, the incidence of which is rising worldwide. Thus, it is not rare to encounter underlying ICAS during EVT procedures, particularly in Asian countries. ELVO due to underlying ICAS is often related to EVT procedure failure or complications, which can lead to poor functional recovery. However, information regarding EVT for this type of stroke is lacking because large clinical trials have been largely based on Western populations. In this review, we discuss the unique pathologic basis of ELVO with underlying ICAS, which may complicate EVT procedures. Moreover, we review EVT data for patients with ELVO due to underlying ICAS and suggest an optimal endovascular recanalization strategy based on the existing literature. Finally, we present future perspectives on this subject.

• Tuberculosis and Respiratory Diseases
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• 제60권6호
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• pp.625-630
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• 2006

배 경: COPD 환자에서 흡연은 폐혈관에 직접 작용하여 혈관 수축, 확장 및 혈관세포 증식을 조절하는 매개물질을 분비하여 혈관의 부적절한 개형 및 생리 현상을 초래하여 폐성고혈압을 유발한다. COPD 환자에서는 종종 급성 및 만성 폐혈전증이 일어나고 혈장내 응고전구물질 및 섬유소용해계의 표지자들이 증가되어 있다. 그러나 COPD 환자에서 혈액 응고계 및 섬유소용해계가 우심실 기능 장애에 어떤 기여를 하는지는 잘 알려져 있지 않다. 본 연구에서는 진행된 COPD 환자에서 multidetector CT scan (MDCT)을 이용하여 측정한 우심실 기능에 따른 혈액내 응고계 및 섬유소용해 계의 변화를 알아보고자 하였다. 방 법: GOLD 지침에 따라 COPD로 진단한 26명에서 심장 MDCT scan을 이용하여 우심실 박출계수를 구하였다. 혈액내 thrombin antithrombin (TAT) 및 plasminogen activator inhibitor (PAI)-1은 enzyme linked immunoassay 방법으로 측정하였다. 결 과: COPD 환자의 혈중 TAT는 $10.5{\pm}19.8{\mu}g/L$으로 정상인의 혈중 TAT $3.4{\pm}2.5{\mu}g/L$보다 의미 있게 증가되었으나 (p<0.01) COPD 환자의 혈중 PAI-1는 $29.6{\pm}20.7ng/mL$으로 정상인의 혈중 PAI-1 $25.9{\pm}17.9ng/mL$와 비교하여 의미 있는 변화가 없었다. COPD 환자에서 혈중 TAT는 MDCT scan으로 측정한 우심실 박출계수와 의미 있는 역 상관관계를 보였으나 (r=-0.645, p<0.01) 혈중 PAI-1은 우심실 박출계수와 상관관계를 보이지 않았다 (r=0.022, p=0.92). 결 론: COPD 환자에서 혈중내 응고계는 활성화되어 있으며 혈중 TAT는 우심실 기능 장애의 의미있는 표지자로 사료된다.

• Reproductive and Developmental Biology
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• 제29권3호
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• pp.187-191
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• 2005

본 연구는 한우 난포란이 체외성숙된 환경의 변화를 단백질 측면으로부터 검토하기 위하여 체외성숙 배지와 세포질내 단백질 변화와 종류를 검토하였다. 그 결과 배지 내의 단백질 발현량은 배양 4.5시간째까지 감소하였고, 배양 13.5시간째까지는 변화가 없었다. 그러나 배양 $13.5\~18$시간 사이에 증가한 후 배양 18시간 이후에 다시 감소하는 경향이었다. 세포질내의 단백질 발현량은 배양 4.5시간째까지 증가하였고 배양 9시간째까지 급격히 감소하였다. 배양 9시간째부터 18시간째 까지는 단백질 발현량이 유사한 경향이었으나 배양 18시간째부터 24시간째까지 다시 증가하였다. 한편 체외성숙한 배지와 세포질을 2차원 전기영동하여 각각 298개 및 35개의 단백질 spot을 확인하였고, 그 중 배지에서는 28개, 세포질에서는 5개의 spot이 유의적인 변화를 확인하였다. 이들 spot 대한MALDI-TOP분석으로 배지와 세포질에서 각각 8개 및 1개의 단백질을 동정하였다. 그 종류는 aldose reductase, alpha enolase, apolipoprotein A-1 precursor, 43M1a collectin precursor, heat shock 27kDa protein, plasminogen activator inhibitor-1 precursor, thrombospondin 1 transitional endoplasmic reticulum ATPase 및 $\beta$-tubulin이었다.

• 대한한방내과학회지
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• 제25권4호
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• pp.18-24
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• 2004

연구배경 : 플라스미노겐 활성 억제인자-1 (plasminogen activator inhibitor-1; PAI-1)은 허혈성 뇌경색의 발생의 원인이 되는 섬유소 용해작용의 저하를 매개하는 인자로서, PAI-1의 작용이 촉진되면 섬유소 용해기능이 저하되어 관상동맥 및 뇌혈관질환의 발생을 증가시키게 된다. PAI-1 유전자의 촉진자(promoter) 영역에는 -675 4G/5G (4G/5G)와A -844G (A/G)의 두 개의 유전자 다형성이 존재하며, 이는 PAI-1의 유전자 전사과정에 영향을 미쳐 혈청 PAI-1의 농도를 증가시키고 결과적으로 허혈성 뇌경색의 발생확률을 높이는 작용을 하게 된다. 연구방법 : 허혈성 뇌경색으로 진단 받은 167명의 환자와 173명의 건강인의 말초혈액에서 DNA를 분리한 후 PAI-1의 4G/5G와 A/G 유전자 다형성에 대한 연쇄중합반응 및 제한효소 절편길이 다형성 (polymerase chain reaction-restriction fragment length polymorphism; PCR-RFLP) 방법을 이용하여 허혈성 뇌경색 발생과 유전자 다형성과의 관계를 비교 분석하였다. 결과 : 허혈성 뇌경색 환자에서의 4G/4G의 유전자형의 빈도는 15.0%으로 정상 대조군의 33.5%에 비해 현저하게 낮게 나타났다 (P < 0.0001). 각각의 유전자형과 허혈성 뇌경색의 발생 위험도 (odd ratio ; OR)와의 관계를 분석했을 때 4G/4G 유전자형을 가질 경우 위험도는 0.35배로 현저하게 낮아졌으며, (P < 0.0001), 5G/5G 유전자형을 가질 경우 위험도는 4.49배 로 현저하게 높아졌다 (P < 0.0001). 그러나, A/G 유전자 다형성과 허혈성 뇌경색의 발생과는 유의한 연관성을 발견하지 못하였다. 결론 : 이상의 결과로 볼 때 PAI-1 유전자의 4G/4G 유전자형은 허혈성 뇌경색의 발생 비율을 감소시키는 작용을 하는 것으로 여겨진다.