• BMB Reports
• /
• 제48권6호
• /
• pp.348-353
• /
• 2015

In the present study, we investigated the characteristics of drug efflux transporter expressions following status epilepticus (SE). In the hippocampus and piriform cortex (PC), vasogenic edema peaked 3-4 days after SE. The expression of breast cancer resistance protein (BCRP), multidrug resistance protein-4 (MRP4), and p-glycoprotein (p-GP) were decreased 4 days after SE when vasogenic edema was peaked, but subsequently increased 4 weeks after SE. Multidrug resistance protein-1 (MRP1) expression gradually decreased in endothelial cells until 4 weeks after SE. These findings indicate that SE-induced vasogenic edema formation transiently reduced drug efflux pump expressions in endothelial cells. Subsequently, during recovery of vasogenic edema drug efflux pump expressions were differentially upregulated in astrocytes, neuropils, and endothelial cells. Therefore, we suggest that vasogenic edema formation may be a risk factor in pharmacoresistent epilepsy. [BMB Reports 2015; 48(6): 348-353]

• Biomolecules & Therapeutics
• /
• 제24권5호
• /
• pp.482-488
• /
• 2016

Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters.

• 자연과학논문집
• /
• 제8권2호
• /
• pp.35-41
• /
• 1996

MCAT1 의 기질과 결합하는 장소를 조사하기 위해 세포막내에 존재하는 부분의 극성 아미노산을 반대 극성의 아미노산으로 치환시킨 돌연변이체를 만들어 arginine 통과능력, gp70 결합능, efflux, Xenopus oocyte 를 이용한 단백질 발현 능력등을 조사하였다. 다섯 개의 돌연변이체중 D403K 이 가장 흥미로운 성질을 나타냈는데, 그것은 정상적인 gp70 결합능력과 낮은 arginine 통과능력을 나타냈다는 것으로 정상적인 단백질이 세포막에서 발현되고 있으나 arginine 통과능력이 감소했다는 사실을 나타내는 것이다. K211E 를 제외한 모든 돌연변이체가 감소된 arginine efflux 와 감소된 Vmax 값을 나타내었다. 이들 결과로부터 MCAT1 의 403 번째 아미노산인 glutamic acid 가 세포막내에서 기질과 상호작용하는 장소라는 가능성을 시사하였다.

• Archives of Pharmacal Research
• /
• 제10권2호
• /
• pp.80-87
• /
• 1987

To get a better insight into the exxistence and the role of a Na-Ca exchange mechanism in smooth muscle, the effect of Na substitution with sucrose on tension development, cellular Ca uptake and $^{45}Ca$ efflux was investigated using isolated cat ileal longitudinal muscle strips. Experimental results were summarized as follows;1) Exposure of the cat ileal longitudinal muscle to Na-free solution induced a contraction, and the magnitude of the contraction increased after incubation of the muscle strips with ouabain ($2{\times10^{-}5}$M) for 1hr. 2) Cellular Ca uptake in Na-free solution increased with an increase in Na content of the Na-loading media, and a linear relationship existed between tissue Na content and cellular Ca uptake for 10 min 3) After tissues were equilibrated in PSS containing $^{45}Ca$ for 2hr, cellular Ca uptake decreased with rising the external Na concentration. 4)Removal of medium Na or inhibition of the Na-K pump decreased the rate of $^{45}Ca$ efflux. These results strongly suggested that Na substitution increases cellular Ca uptake and decreases the rate of $^{45}Ca$ efflux via a Na-Ca exchange mechanism.

• BMB Reports
• /
• 제51권2호
• /
• pp.98-103
• /
• 2018

Recurrence is a serious problem in patients with bladder cancer. The hypothesis for recurrence was that the proliferation of drug-resistant cells was reported, and this study focused on drug resistance due to drug efflux. Previous studies have identified FOXM1 as the key gene for recurrence. We found that FOXM1 inhibition decreased drug efflux activity and increased sensitivity to Doxorubicin. Therefore, we examined whether the expression of ABC transporter gene related to drug efflux is regulated by FOXM1. As a result, ABCG2, one of the genes involved in drug efflux, has been identified as a new target for FOXM1. We also demonstrated direct transcriptional regulation of ABCG2 by FOXM1 using ChIP assay. Consequently, in the presence of the drug, FOXM1 is proposed to directly activate ABCG2 to increase the drug efflux activation and drug resistance, thereby involving chemoresistance of bladder cancer cells. Therefore, we suggest that FOXM1 and ABCG2 may be useful targets and important parameters in the treatment of bladder cancer.

• Ecology and Resilient Infrastructure
• /
• 제8권1호
• /
• pp.32-43
• /
• 2021

삼림 생태계에서 토양 CO2 유출량의 연속적인 모니터링을 위한 다중채널 자동챔버시스템 (MCACs)을 개발하였다. MCACs는 자동개폐 덮개가 있는 8개의 토양챔버, 8개의 다중채널 가스샘플러를 장착한 적외선 CO2 농도 분석기, 시간 릴레이 회로를 갖춘 전자 컨트롤러, 프로그래밍이 가능한 로직용 자료수집장치로 구성되었다. 사계절 장기간에 걸쳐 야외 현장에서 MCACs의 안전성과 신뢰도를 조사하고, 높은 시간분해능으로 현장 테스트에서 얻은 온도와 토양수분 함량이 토양 CO2 유출에 미치는 효과들을 파악하기 위해, 2010년 1월부터 12월 사이의 기간 동안 남산의 신갈나무림 실험지소에서 MCACs를 사용하여 토양 CO2 유출속도와 미기상 요인들을 지속적으로 측정하였다. 토양 CO2 유출속도의 일변화 및 계절적인 변화는 현저하게 온도 요인의 경향을 따랐다. 전체 실험 기간 동안에 토양 CO2 유출속도는 5 cm 깊이의 토양온도와 밀접한 상관관계 (r2 = 0.92)를 보였으나 토양수분 함량과는 약한 상관관계 (r2 = 0.27)를 나타냈다. 남산 신갈나무림에서 온도에 대한 토양 CO2 유출량의 연간 민감도(Q10 수치)는 2.23~3.0의 범위에 달했고, 다양한 온대지역의 낙엽활엽수림에 대한 다른 연구들과 일치하였다. MCACs에 의해 측정된 연평균 토양 CO2 유출량은 약 11.1 g CO2 m-2 day-1이었다. 이 결과들은 MCACs가 야외 현장에서 토양 CO2 유출량의 연속적인 장기측정과 동시에 미기상 요인들의 영향을 결정하는데 유용한 시스템임을 나타낸다.

• Journal of Applied Biological Chemistry
• /
• 제63권1호
• /
• pp.35-41
• /
• 2020

(-)-epigallocatechin-3-gallate (EGGG), a flavonoid found in green tea, is known to have low bioavailability. In this study, we determine whether piperine, a natural bioenhancer, can increase the absorption rate of EGCG. Using a Caco-2 cell monolayer, permeability experiments were performed in Hanks' balanced salt solution (HBSS) and EGCG stability was adjusted to pH 6.5 and pH 5.5 by ascorbic acid treatment. When HBSS was adjusted to pH 6.5, EGCG remained at 94.78% for up to 2 h and remained at 86.04% after 4 h and the net efflux decreased compared to the control. As a result, uptake was significantly increased in the piperine co-administered group compared to the EGCG-alone group, showing that piperine increased the permeability of EGCG in the Caco-2 cell monolayer. These results suggest that piperine inhibits EGCG glucuronidation and efflux, allowing for greater absorption of EGCG.

• Mycobiology
• /
• 제45권4호
• /
• pp.426-429
• /
• 2017

A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

• 미생물학회지
• /
• 제49권2호
• /
• pp.126-130
• /
• 2013

원유시료에서 분리한 장알균속 세균 245균주의 항생제 내성에 관여하는 다중약물 유출 펌프 유전자 분포도와 항생제 내성 패턴을 연구하였다. 그 결과 245 장알균속 균주의 ampicillin에 대한 내성률은 44.1%, erythromycin에 대한 내성률은 79.2%, tetracycline에 대한 내성률은 76.3%, chloramphenicol에 대한 내성률은 36.3%였으며 vancomycin과 ciprofloxacin에 대해서는 모두 감수성임을 알 수 있었다. 내성 관련 유전자 중 MFS타입의 eme(A)는 82.1%의 장알균에 분포하였으며, ABC 타입의 유전자인 efr(A)는 72.7%, efr(B)는 77.1%, lsa는 71.8%의 장알균에 분포하였다. 특히 이러한 유전자의 기원 세균인 Enterococcus faecalis의 경우 eme(A)는 92.5%, efr(A)는 87.4%, efr(B)는 88.4%, lsa는 88.4%의 분포도를 나타내었다. 한편 동일한 장알균속이지만 종이 다른 장알균에서 eme(A)는 E. faecium 4균주, E. avium 7균주, E. durans 4균주 및 E. raffinosus 2균주에 분포하고 있었다. efr(A)는 E. faecium 2균주와 E. durans 2균주에 분포하였으며, efr(B)는 E. faecium 4균주, E. avium 5균주 및 E. durans 4균주에 분포하였다. 본 연구는 우리나라 원유시료에서 분리한 장알균속의 여러 종의 세균에서 동일한 다중약물 유출 펌프(multidrug efflux pump)의 분포에 대한 첫 번째 보고라 사료되며 E. faecalis 이외의 장알균속에서 이러한 유전자의 분포는 서로 다른 종간의 유전자의 수평적인 이동의 가능성을 시사한다.

• The Korean Journal of Physiology
• /
• 제28권1호
• /
• pp.79-90
• /
• 1994

The objective of the present study is to assess the contribution of bulk flow to the regulatory mechanism of amniotic fluid volume and its ionic concentration in the membranes surrounding the amniotic fluid. For quantitative assessment, we prepared 4 kinds of artificial amniotic fIuids (isotonic isovolumetric, hypotonic isovolumetric, isotonic hypervolumetric and hypotonic hypervolumetric ones) by replacing 70% of amniotic fluid of pregnant rabbits with water or normal Tyrode solutions. Isoosmotic saline of 0.5 ml volume containing 0.05% Censored and 15 mM/l LiCl was administered initially into amniotic sacs of all subject animals. Samples of amniotic fluid were collected in after 30 and 90 minute intervals; the concentrations of Censored, $Na^+\;and\;Li^+$ were determined and compared. Followings are the results obtained. 1. from isovolumetric and increased Congcord group, we couldn't find significant change in $Li^+\;and\;Na^+$ concentration in isotonic amniotic fluid. However, $Na^+$ concentration increased significantly as well as a striking increase in Censored concentration in hypotonic amniotic fluid. 2. In isovoIumetric and decreased Censored group, the rate of $[Li^+]$ decrement and the rate of $[Na^+]$ increment were much higher in hypotonic amniotic fluid than in isotonic. 3. In hypervolumetric and increased Censored group, the rate of $Na^+$ efflux increased proportionately with the increment of Censored concentration up to 0.98, which was higher than the rate of $Li^+$ efflux in isotonic amniotic fluid. However, the increment of $Na^+$ concentration was rather related with the initial $Na^+$ concentration in hypotonic amniotic fluid, showing inverse relationship. $Li^+$ concentration increased only when there was a marked increase in Censored concentration and approached near a maximum value or 1. 4. For hypervolumetric and decreased Censored group, the observations were identical to isovolumetric and decreased Censored group. From these results the following conclusions could be made: 1) There is no net movement of water or monovalent cations across the membranes surrounding amniotic fIuid in isotonic isovolumetric condition. In contrast, there is a net efflux of amniotic fluid by osmotic bulk flow, resulting in elevation of $Na^+$ concentration in hypotonic isovolumetric condition. 2) In hypervolumetric conditions, there is a massive efflux of amniotic fluid or solvent drag through the surrounding membranes by fiItrative bulk flow, where the rate of $Na^+$ efflux has a linear relationship with that of water efflux. This is assumed to be carried out through enlarged and newly opened intercellular spaces resulting from increased intraamniotic pressure. 3) Once increasing intraamniotic pressure reaches a point allowing $Li^+$ to pass through during osmotic bulk flow in hypotonic amniotic fIuid, $Na^+$ influx seems to occur by diffusion simultaneously or immediately thereafter, too.