• The Korean Journal of Physiology
• /
• 제29권1호
• /
• pp.39-50
• /
• 1995

This study was designed to clarify the action of cyclic nucleotides, cyclic AMP and cyclic GMP, on phorbol 12,13-dibutyrate (PDBu)-induced contraction in rings isolated from rabbit carotid artery. Arterial rings, 2 mm in width, were myographied isometrically in an isolated organ bath. PDBu produced slowly developing, sustained contraction in rabbit carotid artery, in a dose dependent manner, which was independent of extracellular $Ca^{2+}$ PDBu-induced contraction was relaxed by staurosporine, which suggests that PDBu-induced contraction is mediated by protein kinase C (PKC). $^{45}Ca^{2+}$ uptake by rabbit carotid artery was increased by PDBu during depolarization, but not in control. Isoproterenol and sodium nitroprusside (SNP) relaxed phenylephrine-induced contraction. However, SNP but not isoproterenol relaxed the contraction induced by PDBu. Acetylcholine relaxed PDBu-induced contraction in the presence of the endothelium. 8-bromo-cyclic AMP, a permeable analogue of cyclic AMP, suppressed phenylephrine-induced contraction but not PDBu-induced contraction. 8-bromo cyclic GMP relaxed both of them with dose dependency. A large dose of forskolin relaxed PDBu-induced contraction. PDBu increased cyclic AMP without considerable change in the level of cyclic GMP. Based on these findings, PDBu-induced contraction of rabbit carotid artery was relaxed by cyclic GMP more effectively than cyclic AMP, and the action of cyclic AMP could be mediated by cyclic GMP dependent protein kinase. Therefore it is suggested that the antagonistic action between protein kinase C and cyclic GMP-dependent protein kinase plays a major role in the regulation of vascular tone.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2020년도 춘계학술대회
• /
• pp.70-70
• /
• 2020

참취(Aster scaber)는 국화과에 속하는 여러해살이식물로 취나물로 분류되어 전국에서 재배되고 있으며 주로 시설재배지 조기재배 작형으로 많이 재배하고 있다. 참취의 잎과 줄기는 맛과 향기가 독특하여 예로부터 생채, 묵나물 등으로 이용되어 왔으며 칼슘, 철분, 비타민 A 등이 풍부하여 건강식품으로서도 가치가 높고 한약재로도 사용되기도 한다. 최근에는 항암효과와 더불어 콜레스트롤을 저하시키는 약리적 효능이 있는 것으로 밝혀져 기능성 식품으로도 각광 받고 있다. 참취 시설재배 시 통상 3년 마다 갱신이 이루어지고 있는데 그 이유로는 시설재배지 특성상 양분의 과다투입에 의한 염류집적과 잦은 관수로 물리성이 악화되어 참취의 생육이 저하되어 수량이 감소하는 결과를 초래한다. 본 연구는 토양개량제 처리에 따른 토양 물리화학성과 참취의 생육에 미치는 영향을 검토하여 참취 시설재배 농가에 활용할 수 있는 방안을 개발하고자 시험을 수행하였다. 2018년 4월부터 2020년 7월까지 전라북도 농업기술원 허브산채시험장에서 참취 시설재배를 대상으로 무처리, 볏짚 1,000kg/10a, 왕겨숯 1,000kg/10a, 야자섬유 1,000kg/10a, 4처리구로 하여 시기별 토양특성 변화 및 생육 상황을 조사하였다. 자재 처리 후 3년차 토양 물리성의 변화는 볏짚 시용에서 가장 낮은 용적밀도 1.23g/cm³와 가장 높은 공극률 53.50%을 보였다. 토양 삼상은 고상은 왕겨숯에서 49.41%로, 액상은 왕겨숯에서 24.92%로, 기상은 볏짚에서 32.09%로 가장 높았다. 토양화학적 특성을 조사한 결과 토양 pH는 7.2~7.3, 토양유기물 함량은 32~39g/kg, 유효인산 함량은 440~487mg/kg 이었으며 처리 전 토양에 비하여 유기물 함량은 증가하고 유효인산은 낮아지는 경향을 보였다. 치환성 양이온 K, Ca, Mg는 K는 0.77~0.88cmolc/kg로 낮아졌고, Ca와 11.56~14.09cmolc/kg, Mg는 2.93~3.22cmolc/kg로 증가하였다. 참취 생육특성은 초장은 24.8~26.4cm, 엽장은 8.3~8.7cm, 엽폭은 6.3~6.7cm, 줄기수는 6.9~7.2주로 대조구에 비해 좋은 생육 상황 상황을 보였으며, 수량은 919~1,161kg/10a 으로 자채 처리구에서 대조구에 비해 수량성 또한 높았다 참취 다년재배지 토양개량제 시용함으로써 토양의 유기물함량 증가와 토양의 용적밀도 감소와 토양 공극율 증가 등 토양의 물리화학성을 개선할 수 있을 것으로 기대된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권6호
• /
• pp.521-531
• /
• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Biomolecules & Therapeutics
• /
• 제28권4호
• /
• pp.370-379
• /
• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• 대한한의학회지
• /
• 제19권1호
• /
• pp.251-270
• /
• 1998

The effects of Gamigunshimtang on the isolated perfused ischemic heart in rats, heart rates, left ventricular pressure, cardiac blood flow and cardiotoxicity were stu.died in H9C2 myoblast cell, myocardial slice culture The results were as follows: 1. The administration of Gamigunshimtang to the rat recovered effectively heart rate, left ventricular pressure and flow rate from the experimental ischemia in perfused rat heart. The release of lactic dehydrogenase after the ischemia also decreased compared to the control group. 2. The administration of Gamigunshimtang to H9C2 myoblast culture enhanced the cell proliferation and protected against doxorubicin and allylamine induced release of the lactic dehydrogenase into the culture medium. It also protected effectively against doxorubicin and allylamine induced decrease of Ca ATPase activity and the increase of NADPH-cytochrome C reductase activity in the microsome. 3. The administration of Gamigunshimtang to the rat myocardial slice culture protected effectively against doxorubicin and allylamine induced decreases of protein synthesis and ATP content, and increases of cvtosolic enzyme, creatin kinase into the medium and lipid peroxidation.

• Biomolecules & Therapeutics
• /
• 제30권1호
• /
• pp.48-54
• /
• 2022

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα_i/o and Gα_q/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca²⁺ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

• Biomolecules & Therapeutics
• /
• 제30권3호
• /
• pp.265-273
• /
• 2022

Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil-resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G₁ cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca²⁺ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box-binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonin-induced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil-resistant colorectal cancer.

• 대한의생명과학회지
• /
• 제28권3호
• /
• pp.200-205
• /
• 2022

Established cancer cell lines are widely used for developing biomarkers for the patient-specific treatment of colorectal cancer and predicting prognoses. However, cancer cell lines may exhibit different drug responses depending upon the characteristics of the cell line. Therefore, it is necessary to select a tumor cell line suitable for the purpose of the study by considering the cell characteristics. This study investigated the levels of CXCL10, which were recently been reported to play an important role in the outcome of tumor treatment, secreted by colon cancer cells. 2 × 10⁵ cells/mL of each colorectal cancer cell was seeded into a 35 mm cell culture dish. After 24 h incubation, culture supernatant was used to determine the secreted CXCL10 levels. Among six colorectal cancer cell lines (HT-29, HCT116, CaCo-2, SW620, SW480, and CT26), Caco-2 cells showed the highest level of CXCL10 secretion. HT-29 cells showed the second-highest level of CXCL10 secretion. No significantly measurable level of CXCL10 secretion was detected in HCT116 cells. These results will be helpful in investigating the molecular basis of colorectal cancer.

• 한국식품과학회지
• /
• 제36권2호
• /
• pp.321-328
• /
• 2004

오디 과실을 이용한 고부가가치의 가공식품의 개발에 관한 연구 일환으로 먼저 최소가공기술을 이용한 오디 과실주스 제조 방법을 조사하였다. 오디 과실의 물추출액을 면포여과, 감압여과(Whatman No. 4 filter paper를 이용한) 및 원심분리를 각각 실시한 결과 원심분리가 가장 좋은 청징효과를 나타내었다. 그리고 여러 여과보조제 및 청징제를 첨가한 후 원심분리하여 얻은 오디 과실즙의 색의 변화는 처리한 여과보조제, 청징제 및 청징 효소의 종류에 따라 차이가 있었으며, 특히 casein, gelatin, chitin, chitosan 및 PVPP는 오디 색소를 강하게 흡착하였으며, 그리고 청징효소 중 ${\alpha}-amylase$ 처리구가 가장 좋은 청징효과를 나타내었다. 다음, 오디 과즙을 원심분리한 후 $0.01\;{\mu}m$ 막여과를 실시한 결과 오디주스의 청징효과가 매우 우수하였으나 한외여과방법은 오디 색소의 강한 흡착으로 적절하지 않았다. 한편, 4가지 갈변저해제 처리에 따른 오디 과실주스의 갈변억제 효과를 측정한 결과 200ppm sodium hydrosulfite 처리구가 가장 갈변억제 효과가 우수하였으며, 아울러 0.1% L-ascorbic acid(L-AsA) 및 citric acid(CA)도 갈변억제 효과가 있었다. 그리고 위의 3가지 갈변저해제를 2중 복합병행 처리한 결과 0.1% L-AsA+0.1% CA 처리구가 가장 좋은 갈변억제 효과를 나타내었다. 마지막으로 관능검사를 실시한 결과 오디주스의 최적 당/산비는 40-50이었으며, 또한 상업적 살균 온도($85-90^{\circ}C$)에서 처리시간은 10분이 가장 적합함을 알 수 있었다.

• Journal of Chest Surgery
• /
• 제42권1호
• /
• pp.28-33
• /
• 2009

배경: 경도이상의 기능성 삼첨판막 폐쇄부전이 있는 경우 삼첨판 성형술이 널리 시행되고 있으며, 판륜링을 이용한 성형술이 우수한 성적을 나타내고 있다. 우리는 새로운 삼차원적 모양의 삼첨판륜링(Edwards $MC^3$ annuloplasty system [Edward LifeSciences, Irvine, CA])을 이용한 삼첨판 성형술의 조기성적을 보고하고자 한다. 대상 및 방법: 2004년 11월부터 2006년 7월까지 삼첨판륜의 확장 및 경도이상의 삼첨판막 폐쇄부전이 있는 72명의 환자에서 Edwards $MC^3$ annuloplasty ring을 이용한 삼첨판 성형술을 시행하였다. 72명의 환자 중, 68명에서 정중흉골절개술을 하였고 4명에서 로봇팔을 이용한 최소절개 개흉술을 시행하였다. 남녀비는 21 : 51이었고 평균 나이는 $53.9{\pm}12.3$세였다. 수술 전 삼첨판막 폐쇄부전은 평균 $2.2{\pm}1.0$도였으며 평균 NYHA functional class는 $3.1{\pm}0.8$, 평균 좌심실박출계수는 $57.0{\pm}9.9$%였다. 결과: 삼첨판막 폐쇄부전과 NYHA functional class는 각각 $0.4{\pm}0.6$, $2.0{\pm}0.7$으로 의미있게 감소하였고 삼첨판막 협착은 없었다(p<0.001). 병원 사망은 1명이 있었으며 술 후 합병증은 3도 블록이 발생하여 영구적 인공심박동기 삽입을 한 경우가 1명이 있었다. 결론: 3차원적 모양의 삼첨판륜링은 장착하기 용이하며 임상적, 심초음파 검사상 단기성적은 우수한 것으로 판단된다. 그러나 이 판막륜링의 장기 성적에 대하여는 연구 대상환자에 대한 정기적인 추적관찰 및 검사가 필요하고 더 많은 임상 적용 및 경험이 필요할 것으로 판단된다.