• Reproductive and Developmental Biology
• /
• v.35 no.3
• /
• pp.221-225
• /
• 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
• /
• v.11 no.4
• /
• pp.205-213
• /
• 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.

• Journal of Animal Reproduction and Biotechnology
• /
• v.34 no.3
• /
• pp.240-246
• /
• 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
• /
• v.47 no.4
• /
• pp.227-232
• /
• 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
• /
• v.41 no.4
• /
• pp.335-339
• /
• 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
• /
• v.53 no.4
• /
• pp.240-240
• /
• 2020

• Korean Journal of Radiology
• /
• v.20 no.5
• /
• pp.739-748
• /
• 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
• /
• v.60 no.6
• /
• pp.625-630
• /
• 2006

Background: Pulmonary hypertension in COPD patients is the result of a direct effect of tobacco smoke on the intrapulmonary vessels with the abnormal production of the mediators that control vasoconstriction, vasodilatation, and vascular cell proliferation, which ultimately lead to aberrant vascular remodeling and physiology. COPD patients are prone to the developmint of an acute and chronic thromboembolism with an elevation of the plasma procoagulant and fibrinolytic markers However, the roles of the coagulation and fibrinolysis system on the right ventricular dysfunction in COPD patients are not well defined. We examined the alteration of the coagulation and fibrinolysis system in COPD patients according to the right ventricular function measured using cardiac multidetector computed tomography (MDCT). Methods: The right ventricular ejection fraction (RVEF) was measured using cardiac MDCT in 26 patients who were diagnosed with COPD according to the definition of the GOLD guideline. The plasma level of thrombin antithrombin (TAT) and plasminogen activator inhibitor (PAI)-1 were measured using an enzyme linked immunoassay. Results: The plasma TAT was markedly elevated in COPD patients ($10.5{\pm}19.8{\mu}g/L$) compared with those of the control ($3.4{\pm}2.5{\mu}g/L$) (p<0.01). However, the plasma PAI-1 in COPD patients ($29.6{\pm}20.7ng/mL$) was similar to that in the controls. The plasma TAT showed a significant inverse relationship with the RVEF measured by the cardiac MDCT in COPD patients (r=-0.645, p<0.01). However, the plasma PAI-1 did not show a relationship with the RVEF (r=0.022, p=0.92). Conclusion: These results suggest that the coagulation system in COPD patients is markedly activated, and that the plasma level of TAT might be a marker of a right ventricular dysfunction in COPD patients.

• Reproductive and Developmental Biology
• /
• v.29 no.3
• /
• pp.187-191
• /
• 2005

This study was designed to investigate the changes of quantity and quality of proteins in medium and cytoplasm during in vitro maturation of bovine oocytes. The total quantity of proteins in medium decreased from 0 to 4.5 hr, but increased from 13.5 to 18 hr after the onset of in vitro maturation. The total quantity of protein in cytoplasm increased from 0 to 4.5 hr, decreased from 4.5 to 9 hr, and increased after 18 hr after the onset of in vitro maturation. A total of 298 protein spots was detected on a gel of 2D SDS-PAGE form maturation medium. Among 28 protein spots expressed significant differences in their quantity, 8 proteins were identified by peptide mass fingerprinting (aldose reductase, alpha enolase, apolipoprotein A-1 precursor, 43kDa collectin precursor, heat shock 27kDa protein, plasminogen activator inhibitor-1 precursor, thrombospondin 1, transitional endoplasmic reticulum ATPase). Among total of 35 protein spots detected on gel of 2D SDS-PACE from oorytes cytoplasm, $\beta$-tubulin was identified by peptide mass fingerprinting.

• The Journal of Internal Korean Medicine
• /
• v.25 no.4
• /
• pp.18-24
• /
• 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.