Effects of DK-002, a synthesized (6aS,cis)-9,10-Dimethoxy-7,11b-dihydro-indeno[2,1-c]chromene-3,6a-diol, on platelet activity

Lee, Ki-Seon,Khil, Lee-Yong,Chae, Sang-Ho,Kim, Deukjoon,Lee, Byung-Hoon,Hwang, Gwi-Seo,Moon, Chang-Hyun,Chang, Tong-Shin,Moon, Chang-Kiu 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.17

In the present study, the mechanism of antiplatelet activity of DK.-002, a synthesized (6aS,cis)-9.10-Dimethoxy-7,11b-dihydro-indeno|2,1-c ]chroniene-3.6a-diol, was investigated. DK-002 inhibited the thrombin, collagen, and ADP-induced rat platelet aggregation in a concentration- dependent manner, with 1C_(50) values of 120. 27, and 47 μM, respectively. DK-002 also inhibited thrombin-induced dense granule secretion, thromboxane A_(2) synthesis, and [Ca^(2+)], elevation in platelets. DK-002 did not show any significant effect on ADP-induced inhibition of cyclic AMP elevation by prostaglandin E_(1). but DK-002 was confirmed to inhibit ADP-induced [Ca^(2+)] elevation and shape change. DK-002 inhibited 4- bronw-A23187-induced [Ca^(2+)], elevation in the presence of creatine phosphate/creatine phosphokinase (CP/CPK, a ADP scavenging system) and indomethacin (a specific inhibitor of cyclooxygenase). DK-002 also inhibited Ca^(2+) mobilization in thrombin- or 4-bromo-A23187-stimulated platelets through its inhibitory effects on both Ca^(2+) release from intracellular stores and Ca^(2+) influx, in the presence of CP/CPK and indomethacin. Taken together, the present study shows that DK-002 has inhibitory effects on stimulation of platelets, and suggests that its antiplatelet activity might be related to the inhibitory mechanism on Ca^(2+) mobilization in stimulated platelets. ⓒ 2005 Elsevier Inc. All rights reserved.

여성 복압성 요실금에서 질전벽슬링수술의 효과

신홍석,유진욱,정희창,박동춘 영남대학교 기초/임상의학연구소 2001 Yeungnam University Journal of Medicine Vol.18 No.1

Background: The purpose of this study was to determine the efficacy and safety of the anterior vaginal wall sling in the management of women with stress urinary incontinence. Materials and Methods: From January 1998 to December 1999, 42 patients(31 with genuine stress urinary incontinence and 11 with mixed urinary incontinence, 38 with anatomical incontinence and 4 with intrinsic sphincteric deficiency) underwent anterior vaginal wall sling at Yeungnam University Hospital were studied retrospectively. The mean age was 49.3 years(ranging from 34 to 66 years of age) and the mean follow-up period was 29.4 months(ranging from 16 to 40 months). Intra- and postoperative complication, success rate and patient's satisfaction were evaluated. Results: The mean operation time was 79 minutes(ranging from 65 to 124 minutes) and the mean hospital stay was 5.1 days(ranging from 4 to 10 days). Mean postoperative Foley catheter drainage was 2.1 days(ranging from 1 to 5 days). As a complication, bladder perforation occurred in one patient(2.4%), residual urine sensation developed in seven patients(16.7%), and suprapubic pain was complained in five patients(11.9%), which improved gradually. Vaginal epithelial inclusion cyst occurred in one patient(2.4%) at postoperative 31 months. Four(9.4%) patients with de novo instablility were improved by anticholinergics medication. The success rate was 92.9% and 38 patients(90.5%) were satisfied with this procedure. Conclusion: We consider that the anterior vaginal wall sling to be a safe and effective surgical procedure for the treatment of female stress urinary incontinence, but a longer follow-up is necessary to determine long term effect.

사염화탄소의 간독성에 대한 파두 다당류분획의 예방효과

이은경,길이룡,소동수,창동신,전선덕,정명규,문창규 한국환경독성학회 1996 환경독성보건학회지 Vol.11 No.2

In present study, we fractionated polysaccharides from Croton tiglium and investigated their hepatoprotective effects on CCI₄ intoxication. Polysaccharide fraction of which molecular weight is over 300,000(HP) showed the most potent hepatoprotective effects on CC1₄ intoxication. Lipid peroxidation, BAST and sALT were used as parameters to evaluate the liver damage. Glucose, xylose and arabinose were found to be monosaccharides composing sugar moiety of HP.

Alloxan 유도 당뇨병상태에서 과산화지질생성에 미치는 Brazilin의 효과

안영수,길이룡,소동수,창동신,김진형,박광식,문창규 한국환경독성학회 1996 환경독성보건학회지 Vol.11 No.2

Brazilin was tested for its ability to inhibit alloxan induced lipidperoxidation. Lipid peroxide contents in liver, kidney and serum were measured by the TBA method. ICR mice receiving alloxan at a dose of 43mg/kg via the tail vein after a 24hrs starvation showed significantly increased lipid peroxide contents as compared to untreated control. Lipid peroxide contents in liver, kidney and serum of alloxan-induced diabetic mice were dose-dependently decreased by the treatment of brazilin at a dose of 10mg/kg, 50mg/kg, 100 mg/kg for 5 days.

Screening and Development of Peroxiredoxin inhibitor as anticancer agent

Chang, Tong-Shin 이화여자대학교 세포신호전달연구센터 2009 고사리 세포신호전달 심포지움 Vol. No.11

Most cancer cells exhibit the increase in reactive oxygen species(ROS) generation, which enable to maintain their malignant phenotypes. Cancer cells, under oxidative stress associated with increased metabolic activity and production of ROS, are highly dependent on antioxidant system for survival and thus more susceptible to exogenous oxidative insults by ROS-stressing agents than normal cells. Peroxiredoxin(Prx), the novel H₂O₂ scavenging protein, is known to be elevated in a variety of human cancers. Abnormal increase in ROS which was induced by the inhibition of Prx can cause cellular damage and trigger cell death in cancer cell. Through a chemical screening a library of ~25,000 small molecules, we have identified nine positive hits as Prx I inhibitors. The selected compounds have the similar chemical scaffolds. In this study, we chose to focus on compound #59(C59) because it had shown the best inhibitory effect on cancer cell growth. C59 causes severe ROS accumulation and oxidative mitochondrial damage, and then induces cell death in A549 human lung adenocarcinoma. Oncogenic transformation of ovarian epithelial cells with H-Ras^(V12) causes elevated ROS generation and renders the malignant cells highly sensitive to C59, which causes severe ROS accumulation preferentially in the transformed cells. Excessive ROS causes oxidative mitochondrial damage and massive cell death. This study suggests that the Prx-mediated H2O2 scavenging may serve as a novel therapeutic target for cancer intervention by small compounds.

Effect of Hydroxybrazilin on Glutathione Depletion Induced by BrCCl₃ and Menadione in Cultured Rat Hepatocytes

Chang, Eun-Sook,Kim, Seong-Gon,Khil, Lee-Yong,So, Dhong-Su,Chang, Tong-Shin,Kim, Jin-Hyoung,Jeon, Sun-Duck,Park, Kwang-Sik,Moon, Chang-Kiu 한국환경독성학회 1996 환경독성보건학회지 Vol.11 No.2

In this study we investigated the effect of hydroxybrazilin on glutathione depletion induced by BrCCI₃ and menadione in cultured hepatocytes to understand the cellular mechanisms of hepatoprotective effect of hydroxybrazilin. Iydroxybrazilin alone had no effect on total glutathione level and the ratio of reduced glutathione/total glutathione (GSH/(GSSG+GSH)). BrCCI₃ dramatically decreased total glutathione level and hydroxybrazilin significantly prevented glutathion depletion by BrCCI₃. The ratio of GSH/(GSSG+ GSH) was also decreased by BrCCI₃ and recovered by hydroxybrazilin treatment. Menadione decreased total glutathione level and the ratio of GSH/(GSSG+GSH) but hydroxybrazilin showed no significant effects on menadione- induced glutathione depletion. These data suggest that hydroxybrazilin might prevent the hepatotoxicity induced by chemical-derived radicals but not the toxicity linked with oxidative stress.

Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin Ill

Chang, Tong Shin,Noh, You Hyun,Baek, Jin Young,Rhee, Sue Goo,Jeong, Woo Jin 이화여자대학교 약학연구소 2010 藥學硏究論文集 Vol.- No.20

The mitochondria are the major intracellular source of reactive oxygen species (ROS), which are generated during cellular respiration, The role ofperoxiredoxin (Prx) III, a 2-Cys Prx family member, in the scavenging of mitochondrial H₂0₂ has recently been emphasized, While eliminating H₂0₂, Prx can become overoxidized and inactivated by modifying the active cysteine into cysteine sulfinic acid-(Cys-S0₂H). When 2-Cys Prxs are inactivated in vitro, sulfiredoxin (Srx) reduces the cysteine sulfinic acid to cysteines. However, whereas Srx is localized in the cytoplasm, Prx III is present exclusively in the mitochondria. Although Srx reduces sulfinic Prx III in vitro, it remains unclear whether the reduction of Prx III in cells is actually mediated by Srx. Our gain- and loss-of-function experiments show that Srx is responsible for reducing not only sulfinic cytosolic Prxs (I and II) but also sulfinic mitochondrial Prx III. We further demonstrate that Srx translocates from the cytosol to mitochondria in response to oxidative stress. Overexpression of mitochondrion-targeted Srx promotes the regeneration of sulfinic Prx III and results in cellular resistance to apoptosis, with enhanced elimination of mitochondrial H₂0₂ and decreased rates of mitochondrial membrane potential collapse. These results indicate that Srx plays a crucial role in the reactivation of sulfinic mitochondrial Prx III and that its mitochondrial translocation is critical in maintaining the balance between mitochondrial H₂0₂ production and elimination

Switchable redox activity by proton fuelled DNA nano-machines

Shin, Su Ryon,Lee, Chang Kee,Lee, Sun Hee,Kim, Sun I.,Spinks, Geoffrey M.,Wallace, Gordon G.,So, Insuk,Jeong, Ju-Hong,Kang, Tong Mook,Kim, Seon Royal Society of Chemistry 2009 Chemical communications Vol.2009 No.10

<P>The switching electrochemical property of an SWNT/DNA hybrid can be produced through reversible conformational changes between the closed and open state originating from the pH-responding i-motif DNA which significantly improves its molecular switching and stability by hydrophobic interactions with SWNTs.</P> <P>Graphic Abstract</P><P>The switching electrochemical property of an SWNT/DNA hybrid can be produced through reversible conformational changes between the closed and open state originating from the pH-responding i-motif DNA which significantly improves its molecular switching and stability by hydrophobic interactions with SWNTs. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b820634a'> </P>

Regulation of Peroxiredoxin Ⅰ Peroxidase Activity by Cdc2-dependent phosphoarylation

Chang, Tong-Shin,Jeong, Woojin,Kang, Sang Won,Choi, Soon Young,Rhee, Sue Goo 이화여자대학교 세포신호전달연구센터 2001 고사리 세포신호전달 심포지움 Vol. No.3

Recent evidence suggests that H₂O₂ mediates a variety of cellular responses, including proliferation and differentiation, to many important physiological stimuli. Peroxiredoxin(Prx) is a novel family of peroxidase that exists in multiple isoforms in mammalian cells. Prx Ⅰ and Prx Ⅱ, which exist mainly in the cytosol, are also detected in the nuclei fraction prepared from He La and NIH3T3 cells. Prx Ⅰ and Prx Ⅱ contain a consensus site(Thr90-Pro-Lys-Lys93) for phosphorylation by Cdc2, a major regulator of G₂/M transition in the eukaryotic cell cycle. In this study, we investigated the biological function of Prx Ⅰ phosphorylation by Cdc2 during cell cycle progression. The ability of Cdc2 to phosphorylate Prx Ⅰ was confirmed by in vitro kinase assay with a highly purified Cdc2-cyclin B complex or Cdc2 immunocomplex prepared from HeLa cells. Using the mutant Prx Ⅰ in which Thr-90 residue had been substituted with Ala, we identified Thr-90 as a residue phosphorylated by Cdc2. Mutation at Thr-90 to Glu or Asp to mimic the phosphorylation state resulted in a marked decrease in peroxidase activity toward H₂O₂. To monitor Prx Ⅰ phosphorylation in intact cells, we prepared rabbit antibodies that specifically bind to the Prx Ⅰ phosphorylated at Thr-90. Using these site-specific, threonine phosphorylation-dependent antibodies, we observed that Thr-90 phosphorylation was readily induced upon activation of Cdc2 by treatment of HeLa cells with okadaic acid and its phosphorylation correlated well with the accumulation of cells in G₂/M phases. Furthermore, cell synchronization studies showed that Thr-90 was highly phosphorylated during mitosis. Thr-90 phosphorylation of Prx Ⅰ in mitotic cells was greatly reduced by the treatment of a specific Cdc2 inhibitor, roscovitine. These results suggest that phosphorylation of Prx Ⅰ by Cdc2 and the resulting inhibition of its peroxidase activity are likely to result in increase in the concetration of H₂O₂ in the nucleus, which might be a critical signaling component in the progression of normal cell division.

Effects of Hydroxybrazilin on Glutathione Depletion Induced by $\textrm{BrCCl}_3$ and Menadione in Cultured Rat Hepatocytes

Chang, Eun-Sook,Kim, Seong-Gon,Khil, Lee-Yong,So, Dhong-Su,Chang, Tong-Shin,Kim, Jin-Hyoung,Jeon, Sun-Duck,Moon, Chang-Kiu,Park, Kwang-Sik The Korean Society of Environmental Toxicology 1996 환경독성보건학회지 Vol.11 No.3

In this study we investigated the effect of hydroxybrazilin on glutathione depletion induced by BrCCl$_3$ and menadione in cultured hepatocytes to understand the cellular mechanisms of hepatoprotective effect of hydroxybrazilin. Hydroxybrazilin alone had no effect on total glutathione level and the ratio of reduced glutathione/total glutathione (GSH/(GSSG+GSH)). BrCCl$_3$ dramatically decreased total glutathione level and hydroxybrazilin significantly prevented glutathion depletion by BrCCl$_3$. The ratio of GSH/(GSSG+ GSH) was also decreased by BrCCl$_3$ and recovered by hydroxybrazilin treatment. Menadione decreased total glutathione level and the ratio of GSH/(GSSG+GSH) but hydroxybrazilin showed no significant effects on menadione-induced glutathione depletion. These data suggest that hydroxybrazilin might prevent the hepatotoxicity induced by chemicalderived radicals but not the toxicity linked with oxidative stress.