• Toxicological Research
• /
• 제34권4호
• /
• pp.333-341
• /
• 2018

Ferulate is a phenolic compound abundant in wheat germ and bran and has been investigated for its beneficial activities. The aim of the present study is to evaluate the efficacy of ferulate against the oxidative stress-induced imbalance of protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs), and serine/threonine protein phosphatase 2A (PP2A), in connection with our previous finding that oxidative stress-induced imbalance of PTKs and PTPs is linked with proinflammatory nuclear factor-kappa B $(NF-{\kappa}B)$ activation. To test the effects of ferulate on this process, we utilized two oxidative stress-induced inflammatory models. First, YPEN-1 cells were pretreated with ferulate for 1 hr prior to the administration of 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). Second, 20-month-old Sprague-Dawley rats were fed ferulate for 10 days. After ferulate treatment, the activities of PTKs, PTPs, and PP2A were measured because these proteins either directly or indirectly promote $NF-{\kappa}B$ activation. Our results revealed that in YPEN-1 cells, ferulate effectively suppressed AAPH-induced increases in reactive oxygen species (ROS) and $NF-{\kappa}B$ activity, as well as AAPH-induced PTK activation. Furthermore, ferulate also inhibited AAPH-induced PTP and PP2A inactivation. In the aged kidney model, ferulate suppressed aging-induced activation of PTKs and ameliorated aging-induced inactivation of PTPs and PP2A. Thus, herein we demonstrated that ferulate could modulate PTK/PTP balance against oxidative stress-induced inactivation of PTPs and PP2A, which is closely linked with $NF-{\kappa}B$ activation. Based on these results, the ability of ferulate to modulate oxidative stress-related inflammatory processes is established, which suggests that this compound could act as a novel therapeutic agent.

• Biomolecules & Therapeutics
• /
• 제5권3호
• /
• pp.278-283
• /
• 1997

DW-166HC ($^{166}$ Holmium ($^{166}$ Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I ($^{165}$ Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC ($^{166}$ Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

• Journal of Microbiology and Biotechnology
• /
• 제30권2호
• /
• pp.279-286
• /
• 2020

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

• 대한약리학회지
• /
• 제32권3호
• /
• pp.433-444
• /
• 1996

본 연구에서는 열충격에 의한 세포내 단백질 변성을 정량하는 방법을 소개하고 있다. Thiol compound인 diamide [azodicarboxylic acid bis (dimethylamide)]는 단백질변성시 노출된 sulfyhydryl기를 cross-link 시킨다. 정상 상태에서는 노출되지 않는 sulfyhydryl group이 변성된 단백질에서는 노출되기 때문에 diamide에 의한 cross-linking이 선택적으로 일어날 것이다. 그러므로 diamide는 변성된 단백질을 "trap"하는 작용을 할 수 있다. 본 연구진은 세포내 열충격후 고분자 단백질 응집물 (high molecular weight protein aggregate, HAA)이 나타남을 비환원 (non reducing) SDS-PAGE에서 관찰하였고 이를 gas flow counter로 scanning하여 정량하였다. 실험 결과 세포에 열충격을 가한후 diamide를 처리하면 HMA가 열충격 용량의존적으로 증가함을 관찰하였다. 이는 HMA의 양을 측정함으로써 열충격에 의하여 변성된 단백질을 정량할 수 있음을 반증한다. 열내성이 유도된 세포와 그렇지 않은 세포를 비교하였을 때 열내성이 유도된 세포에서는 열충격에 의한 HMA의 형성이 억제됨을 관찰하였다. 열충격후 정상온도에서 회복기를 주면서 시간대별로 diamide를 첨가하고 이때 형성된 HMA양을 측정하여, 단백질 원형복구의 역동성을 실험하였다. 그 결과, HMA는 열내성의 유도 여부와 상관없이 빠르게 없어짐을 알 수 있었다. 그러나 열내성이 유도된 세포에서 HSP70 단항체를 electroporation에 의하여 투여하였을 때 HMA가 현저히 증가하였고, 이는 열내성이 유도된 세포에서는 HSP70의 증가에 의하여 HMA생성이 억제되었음을 나타낸다. HSP70 항체를 이용하여 면역침전을 시행한 결과 변성된 세포내 단백질이 HSP70과 같이 침전됨이 관찰되었다. 이 결과는 HSP70 단백질이 변성된 단백질과 일시적으로 결합하여 정상 상태로 돌아가거나 복구될 수 있도록 도와줄 수 있음을 시사한다.

• Journal of Pharmaceutical Investigation
• /
• 제36권6호
• /
• pp.377-383
• /
• 2006

The purpose of the present study was to examine the pharmacokinetic characteristics of arsenic hexaoxide($As_4O_6$), a novel anticancer compound, after i.v. bolus and oral administration in rats. We developed an ICP-Mass based method to analyze arsenic hexaoxide levels in plasma, bile, urine, feces, and tissue and validated the method. Arsenic hexaoxide rapidly disappeared from the plasma by 10 min($\alpha$ phase) after i.v. administration, which was followed by the late disappearance in the $\beta$ phase. The mean plasma half-lives($t_{1/2}$) of arsenic hexaoxide at the a and $\beta$ phase when administered at a dose of 5 mg/kg were 1.57 and 29.8 min, respectively. The maximum plasma concentration($C_{max}$) was 230 ng/mL, after oral administration of arsenic hexaoxide at a dose of 50 mg/kg. The bioavailability, which was calculated from the dose-adjusted ratio, of the oral administered arsenic hexaoxide was 1.61%. Of the various tissues tested, arsenic hexaoxide was mainly distributed in the spleen, lung, liver and kidney after oral administration. Arsenic hexaoxide levels in the spleen or lung at 24 hr after oral administration were higher than those of maximum plasma concentration($C_{max}$). The cumulative amounts of arsenic hexaoxide found in the urine by 48 hr after the administration of 50 mg/kg were 5-fold higher than those in the bile. However, the cumulative amounts in the feces were 10-fold higher compared with those of urine, suggesting that arsenic hexaoxide is mostly excreted in the feces. In conclusion, our observations indicated that arsenic hexaoxide was poorly absorbed from the gastro-intestinal tract to the blood circulation and transferred to tissues such as the spleen and lung at 24 hr after oral administration. Moreover, the majority of arsenic hexaoxide appears to be excreted in the feces by 48 hr after oral administration.

• 한국미생물·생명공학회지
• /
• 제45권2호
• /
• pp.124-132
• /
• 2017

오늘날 해양생물로부터 얻어진 미생물유래의 이차대사물질은 구조적, 생물학적으로 새로운 화합물의 주요한 자원이다. 그 중에서 해면동물과 미생물 관계는 생리활성 물질을 탐색하는데 가장 흥미있는 자원 중 하나로서 주목받아 왔다. 본 연구에서는 서해안 조간대에서 채집된 주황해변해면(Hymeniacidon sinapium)으로부터 분리된 세균 균주(Microbulbifer sp., 127CP-12)를 검토하였다. 배양된 세균은 자주색 색소를 생산하였으며, 색소생산의 최적 배양조건을 조사하였다. 최대 색소생산을 위한 미생물 배양조건은 $25^{\circ}C$, pH 6.0, 3% NaCl임을 알 수 있었다. 추출용매는 에탄올과 메탄올에 비해 아세톤이 더 적절한 것으로 나타났다. 추출된 색소의 주요성분은 HLPC, NMR, MS, 그리고 UV 스펙트럼의 구조 분석을 통해 유용한 생리활성물질인 비올라세인으로 밝혀졌다. 본 연구는 해양미생물이 관여한 대사물질로부터 생리활성물질을 조사하는 연구기법을 서술함과 동시에 오늘날 변화하는 해양환경에서 해면동물과 미생물 관계의 생태학적 의의를 제시하고 있다.

• Journal of the Korean Wood Science and Technology
• /
• 제48권4호
• /
• pp.513-526
• /
• 2020

The existing preservation methods are difficult to be applied to a large dimension log which is needed for making traditional wooden ship 'Jalur' in Riau Province. Novel techniques to provide the use of readily available species to replace traditional species alternative were investigated. These included infusion and a combination of injection and bandage-wrapping methods for preserving living trees of Balam (Macaranga conifera (Rchb.f. & Zoll.) Müll.Arg.) and Bintangor (Calophyllum soulattri Burm.f.). Water-based boron compounds were applied as wood preservatives. In total, 18 discs from the bottom, middle, and top of four trees and two controls were used. Trees undergoing treatment were also used to see how wood anatomical structure might affect the boron penetration. The overall aim was to identify the best method for use in Jalur manufacturing. The results showed that in infused Balam tree where the hose position for the preservative intake was deep (10-15 cm from the bark), no boron compound was observed in the outer sapwood. Combination of injection and bandage-wrapping method gave higher percentage of boron penetration at bottom and middle of Balam tree. However, infused Bintangor showed 100% boron penetration. The larger vessel diameter, the absence of tyloses, and the simple perforation plates in Bintangor wood were likely to have contributed to the higher penetration of boron. The combination of bandage-wrapping and infusion, or alternatively by infusing the living trees close to the bark, and at as low as position in the stem gives better protection when treatments are applied to living trees.

• 대한의용생체공학회:의공학회지
• /
• 제25권5호
• /
• pp.329-334
• /
• 2004

전자후각(I-nose)시스템은, 전통적으로 음식물이나 플라스틱 제재의 생산에서 자동화된 품질관리 시스템에 사용되어 왔으나, 최근 호흡가스 등을 통해 당뇨, 호흡 및 소화기 질환과 감염 등을 검사하는 진단영역으로 그 응용분야를 확대하고 있다 이러한 질병과 연관이 없는 휘발성 유기화합물(volatile organic compound, YOC) 에 대하여 I-nose 의 센서어래이는 센서 물질과 휘발성 화합물 사이의 반응으로 인해 고유한 반응을 보이며, 신호의 profile 에 그 흔적을 남긴다. 본 연구에서는 센서어래이의 반응 신호를 profile 형태로 유지 및 분석함으로써 I-nose 의 가스시료 인식 성능을 보다 향상시킬 수 있는 방법을 제안하였다. 신호의 profile 에는 패턴인식을 위한 기존의 개별적인 특성(feature) 보다 많은 정보가 들어 있으며, 이를 가스의 구분에 효과적으로 이용하기 위해 디지털 영상처리에서 사용되는 패턴 매칭을 응용한time-profile방법을 새롭게 제안하였다. 제안된 방법의 검증을 위해, 반도체 공정에 의해 제작된 16채널의 초소형 가스센서 어래이를 사용해 측정된 8종류의 각기 다른 가스시료들에 대하여, 동종 및 이종 가스간의 매칭의 정도를 산출하였다. 기존의 방법과 비교한 결과 동종과 이종 가스간의 뚜렷한 구별이 가능하여 이를 패턴인식에 사용하면 E-nose의 가스 인식 성능을 향상시킬 것으로 전망된다.

• Journal of Ginseng Research
• /
• 제44권4호
• /
• pp.664-671
• /
• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• Molecules and Cells
• /
• 제38권11호
• /
• pp.991-997
• /
• 2015

Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of ARE-scontaining mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.