Effects of epigallocatechin gallate on CoCl_(2)-induced apoptosis in PC12 cells

Yang, Kyu-Ho,Mo, Hyun-Chul,Choi, Nam-Ki,Kim, Seon-Mi,Kim,Won-Jae 大韓小兒齒科學會 2006 大韓小兒齒科學會誌 Vol.33 No.1

Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride (CoCl_(2)) has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG). a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by CoCl_(2) and effects of EGCG on CoCl_(2)-induced apoptosis in PC12 cells. Administration of CoCl_(2) decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with 100 µM EGCG for 30 min before PC12 cells were exposed to 150 µM CoCl_(2), being resulted in the cell viability and DNA fragmentation being rescued. CoCl_(2) caused morphologic changes such as cell swelling and condensed nuclei, whereas EGCG attenuated morphologic changes by CoCl_(2). EGCG suppressed the apoptotic peak and a loss of Δψ_(m) induced by CoCl_(2). CoCl_(2) decreased Bcl-2 expression but Bax expression was not changed in CoCl_(2)-treated cells. EGCG attenuated the Bcl-2 underexpression by CoCl_(2). CoCl_(2) augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity, a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by CoCl_(2). NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated CoCl_(2)-induced apoptosis in consistent with those of EGCG. These results suggest, that CoCl_(2) induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against CoCl_(2)-induced apoptosis in PC12 cells. 신경세포자멸사는 저산소 및 허혈환경에서 일어나며 이러한 세포죽은 reactive oxidant species (ROS) 생성을 동반함이 알려져있다. 그러나, 저산소 및 허혈환경에서 일어나는 세포자멸사의 기전 및 그 치료방법은 아직 정립되어 있지 않다. CoCl_(2)는 ROS를 생성하는 등 저산소환경과 유사한 조건을 초래하는 것으로 알려져 있다. Epigallocatechin gallate (EGCG)는 녹차의 polyphenol 성분으로서 세포성장과 죽음에 다양한 약리학적 효과를 나타냄이 알려져 있다. 본 연구는 PC12 세포에서 CoCl_(2)에 의한 세포자멸사기전을 밝히고 이에 미치는 EGCG의 효과를 조사하는데 목적이 있다. Cell viability는 MTT 측정으로 조사되었고, DNA fragmentation은 DNA laddering으로 조사되었다. Bcl-2와 Bax발현 정도는 RT-PCR로, caspase-3와 -9의 활성은 spectrophotometer, caspase-8의 활성은 flow cytometry에 의해 측정되었다. 미토콘드리아에서 세포질로 분비된 cytochrome c는 western blot으로, 분해된 DNA 양과 미토콘드리아 세포막전위 (Δψ_(m))는 FACScan으로 조사되었다. CoCl_(2)투여로 PC12 세포수는 용량 및 시간 의존형태로 감소하였고, genomic DNA fragmentation이 발생하였다. CoCl_(2)투여로 야기된 cell viability의 감소와 DNA fragmentation은 EGCG 전처치에 의해 억제되었다. CoCl_(2)은 세포용적팽창과 condensed nuclei 같은 형태적 변화를 일으켰으며, apoptotic peak, Δψ_(m)감소 및 cytochrome c 유리를 야기하였다. EGCG는 CoCl_(2)에 의한 세포형태변화, apoptotic peak, Δψ_(m)소실 및 cytochrome c 유리를 억제시켰다. CoCl_(2)는 Bcl-2 발현을 감소시켰지만, Bax 발현에는 영향을 미치지 않았다. EGCG는 CoCl_(2)에 의해 야기된 Bcl-2 발현 감소를 억제시켰다. CoCl_(2)는 caspase-3, -8, 그리고 -9의 활성을 증가시켰으며, EGCG는 CoCl_(2)에 의한 세포자멸사를 억제시켰다. 본 실험결과는 PC12 세포에서 CoCl_(2)가 미토콘드리아 의존 및 death receptor의존 기전으로 세포자멸사를 일으키며, EGCG는 세포자멸사기전을 억세지킴으로 신경보호기능을 가짐을 시사하였다.

권역심뇌혈관질환센터 사업의 비용-편익 분석

김병호 ( Byung Ho Kim ),감신 ( Sin Kam ),배상근 ( Sang Geun Bae ),김건엽 ( Keon-yeop Kim ),이원기 ( Won Kee Lee ),홍남수 ( Nam-soo Hong ),박형근 ( Hyeung-keun Park ),이혜진 ( Heyjean Lee ),조은정 ( Eun-jung Cho ),채성철 ( Shung C 한국보건정보통계학회(구 한국보건통계학회) 2017 보건정보통계학회지 Vol.42 No.1

Objectives: This study was conducted to investigate economic feasibility of operating Regional Cardiocerebrovascular Centers using cost-benefit analysis. Methods: The current study assessed cost and benefit data collected from nine hospitals which were designated as Regional Cardiocerebrovascular Centers between 2008 and 2010. Results: The operation of Regional Cardiocerebrovascular Centers reduced mortality rate and length of stay due to acute myocardial infarction and stroke and also decreased disability occurred after stroke. The total calculated cost of operating nine Regional Cardiocerebrovascular Centers was 19.85-22.30 billion won and the minimum benefit calculated was 23.98 billion won. Applying the maximum cost and the minimum benefit, the net benefit was 1.68 billion won, which is estimated to 190 million won per Regional Cardiocerebrovascular Center. Conclusions: The present study revealed that the operation of Regional Cardiocerebrovascular Centers was economically beneficial. The benefit would be larger if intangible benefit such as the long-term effects to community hospitals and enhancement of quality of life of patients and their families are considered.

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

Increasing Recovery of Nontuberculous Mycobacteria from Respiratory Specimens over a 10-Year Period in a Tertiary Referral Hospital in South Korea

( Won Jung Koh ),( Bok Soon Chang ),( Byeong Ho Jeong ),( Kyeong Man Jeon ),( Su Young Kim ),( Nam Yong Lee ),( Chang Seok Ki ),( O Jung Kwon ) 대한결핵 및 호흡기학회 2013 Tuberculosis and Respiratory Diseases Vol.75 No.5

Background: The number of patients with pulmonary disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. The aim of this study was to evaluate long-term trends in the NTM recovery rate from respiratory specimens over a 10-year period in a tertiary referral hospital in South Korea. Methods: We retrospectively reviewed the records of mycobacterial cultures of respiratory specimens at Samsung Medical Center from January 2001 to December 2011. Results: During the study period, 32,841 respiratory specimens from 10,563 patients were found to be culture-positive for mycobacteria. These included 12,619 (38%) Mycobacterium tuberculosis and 20,222 (62%) NTM isolates. The proportion of NTM among all positive mycobacterial cultures increased from 43% (548/1,283) in 2001 to 70% (3,341/4,800) in 2011 (p<0.001, test for trend). The recovery rate of NTM isolates from acid-fast bacilli smear-positive specimens increased from 9% (38/417) in 2001 to 64% (1,284/1,997) in 2011 (p<0.001, test for trend). The proportion of positive liquid cultures was higher for NTM than for M. tuberculosis (p<0.001). The most frequently isolated NTM were Mycobacterium avium-intracellulare complex (53%) and Mycobacterium abscessus-massiliense complex (25%). Conclusion: The recovery rate of NTM from respiratory specimens in South Korea has increased steadily.

Contrast Extravasation on Computed Tomography Angiography Imitating a Basilar Artery Trunk Aneurysm in Subsequent Conventional Angiogram-Negative Subarachnoid Hemorrhage: Report of Two Cases with Different Clinical Courses

Won Ho Cho,Hyuk Jin Choi,Kyoung Hyup Nam,Jae Il Lee 대한뇌혈관외과학회 2015 Journal of Cerebrovascular and Endovascular Neuros Vol.17 No.4

Contrast extravasation on computed tomography angiography (CTA) is rare but becoming more common, with increasing use of CTA for various cerebral vascular diseases. We report on two cases of spontaneous subarachnoid hemorrhage (SAH) in which the CTA showed an upper basilar trunk saccular lesion suggesting ruptured aneurysm. However, immediate subsequent digital subtraction angiography (DSA) failed to show a vascular lesion. In one case, repeated follow up DSA was also negative. The patient was treated conservatively and discharged without any neurologic deficit. In the other case, the patient showed sudden mental deterioration on the third hospital day and her brain CT showed rebleeding. The immediate follow up DSA showed contrast stagnation in the vicinity of the upper basilar artery, suggestive of pseudoaneurysm. Double stents deployment at the disease segment was performed. Due to the frequent use of CTA, contrast extravasation is an increasingly common observation. Physicians should be aware that basilar artery extravasation can mimic the appearance of an aneurysm.

Analysis of the Phenolic Content and Antioxidant Activities of Soybean Extracts from Different Regions and Cultivars

Nam, Jung-Hwan,Kang, Suk-Woo,Hong, Su-Young,Kim, Su-Jeong,Jin, Young-Ik,Kim, Hyun-Sam,Yoon, Young-Ho,Jeong, Jin-Cheol,Pan, Cheol-Ho,Um, Byung-Hun,Nho, Chu-Won,Ok, Hyun-Choong The Plant Resources Society of Korea 2014 한국자원식물학회지 Vol.27 No.6

Phenolic compounds such as isoflavones contribute to the antioxidant properties of soybean. This study investigated differences in the phenolic content and antioxidant activity of ten soybean cultivars grown in two different locations in Korea. We observed a wide range of variation in total isoflavone and phenolic content by location and cultivar. The total isoflavone content of cultivars grown at Pyeongchang (sub-highland) was significantly higher than that in cultivars grown at Gangneung (lowland). In contrast, the total phenolic content of cultivars grown at Gangneung was greater than that of cultivars grown at Pyeongchang. The radical scavenging activity of DPPH was similar to that of the total phenolic content rather than that of the total isoflavone content. These results suggest that antioxidant activity of soybean was associated with phenolic compounds rather than isoflavones. To identify the individual antioxidant components, we used an on-line HPLC-$ABTS^+$-based assay system, ESI/MS, and NMR. The results showed that the strongest antioxidant activity was linked to epicatechin.

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve

Won, Ki-Bum,Nam, Chang-Wook,Cho, Yun-Kyeong,Yoon, Hyuck-Jun,Park, Hyoung-Seob,Kim, Hyungseop,Han, Seongwook,Hur, Seung-Ho,Kim, Yoon-Nyun,Park, Sang-Hyun,Han, Jung-Kyu,Koo, Bon-Kwon,Kim, Hyo-Soo,Doh, J The Korean Academy of Medical Sciences 2016 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.31 No.12

<P>Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank <I>P</I> = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; <I>P</I> = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; <I>P</I> = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; <I>P</I> = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.</P>

Development of Two-Step Temperature Process to Modulate the Physicochemical Properties of β-lactoglobulin Nanoparticles

Ho-kyung Ha,Gyeong-won Nam,Dongwoo Khang,Sung Jean Park,Mee- Ryung Lee,Won-jae Lee 한국축산식품학회 2017 한국축산식품학회지 Vol.37 No.1

The development of a new manufacturing process, a two-step temperature treatment, to modulate the physicochemical properties of nanoparticles including the size is critical. This is because its physicochemical properties can be key factors affecting the cellular uptake and the bioavailability of bioactive compounds encapsulated in nanoparticles. The aims of this study were to produce (beta-lactoglobulin) β-lg nanoparticles and to understand how two-step temperature treatment could affect the formation and physicochemical properties of β-lg nanoparticles. The morphological and physicochemical properties of β-lg nanoparticles were determined using atomic force microscopy and a particle size analyzer, respectively. Circular dichroism spectroscopy was used to investigate the secondary structure of β-lg. The surface hydrophobicity and free thiol groups of β-lg were increased with a decrease in sub-ambient temperature and an increase in mild heat temperature. As sub-ambient temperature was decreased, a decrease in α-helical content and an increase in β-sheet content were observed. The two-step temperature treatment firstly involved a sub-ambient temperature treatment from 5 to 20ºC for 30 min, followed secondly by a mild heat temperature treatment from 55 to 75ºC for 10 min. This resulted in the production of spherically-shaped particles with a size ranging from 61 to 214 nm. Two-way ANOVA exhibited the finding that both sub-ambient and mild heat temperature significantly (p

The Methods to Improve the Wide Dynamic Range using InGaP/GaAs HBT MMIC Double Balanced Mixer for ICS System

Won Yong Cho,Jeong Heo,Se Hwan Kim,Jae Ho Yoon,Sang Hoon Cheon,Bhanu Shrestha,Nam-Young Kim 한국통신학회 2006 한국통신학회 학술대회논문집 Vol.2006 No.7

Enhancement of efficient incorporation of Unnatural Amino Acid by control of translation key factors

Nam Young Kim(김남영),Jin Ho Ahn(안진호),Tae Wan Kim(김태완),In Seok Oh(오인석),Jung won Keum(금정원),Jeong Mi Son(손정미),Dong Myung Kim(김동명),Chang Kil Park(박창길),Cha Yong Choi(최차용) 한국생물공학회 2004 한국생물공학회 학술대회 Vol.2004 No.10