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Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells
Yun-Hee Bae,Jong Hyo Ryu,Hyun-Joo Park,Kwang Rok Kim,Hee-Jun Wee,Ok-Hee Lee,Hye-Ock Jang,Moon-Kyoung Bae,Kyu-Won Kim,Soo-Kyung Bae 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4
Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.
Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells
Bae, Yun-Hee,Ryu, Jong Hyo,Park, Hyun-Joo,Kim, Kwang Rok,Wee, Hee-Jun,Lee, Ok-Hee,Jang, Hye-Ock,Bae, Moon-Kyoung,Kim, Kyu-Won,Bae, Soo-Kyung The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4
Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.
( Hee Kyoung Kang ),( Sang Chul Han ),( Eun Sook Yoo ),( Gyeoung Jin Kang ),( Jong Woo Ock ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.2
Citnrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported activity of flavonoids contained in immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is and anti-inflammatory component in immature C. unshiu.
Silencing of MUC8 by siRNA increases P2Y<sub>2</sub>-induced airway inflammation
Cha, Hee-Jae,Jung, Min-Su,Ahn, Do Whan,Choi, Jang-Kyu,Ock, Mee Sun,Kim, Kyung Soo,Yoon, Joo-Heon,Song, Eun Ju,Song, Kyoung Seob American Physiological Society 2015 American Journal of Physiology: Lung cellular and Vol.308 No.6
<P>Mucin hypersecretion and overproduction are frequent manifestations of respiratory disease. Determining the physiological function of airway mucin is presently considered more important than identifying the relevant signaling pathways. The lack of a full-length human mucin 8 (MUC8) cDNA sequence has hindered the generation of a Muc8 knockout mouse line. Thus, the precise physiological functions of MUC8 are unclear. Herein, we investigated the function of MUC8 using a small-interfering RNA (siRNA)-mediated genetic silencing approach in human airway epithelial cells. Herein, intracellular IL-1α production was stimulated by an ATP/P2Y<SUB>2</SUB> complex. While ATP/P2Y<SUB>2</SUB> increased IL-1α secretion in a time-dependent manner, treatment with P2Y<SUB>2</SUB>-specific siRNA significantly decreased IL-1α secretion. Moreover, ATP increased P2Y<SUB>2</SUB>-mediated upregulation of <I>MUC8</I> expression; however, IL-1α significantly decreased the extent to which ATP/P2Y<SUB>2</SUB> upregulated <I>MUC8</I> expression. Interestingly, treatment with MUC8-specific siRNA decreased the production of anti-inflammatory cytokines (TGF-β and IL-1 receptor antagonist) and increased the production of inflammatory cytokines (IL-1α and IL-6) in our system. In addition, siRNA-mediated knockdown of MUC8 expression dramatically increased the secretion of inflammatory chemokines and resulted in an approximately threefold decrease in cell chemotaxis. We propose that MUC8 may function as an anti-inflammatory mucin that participates in inflammatory response by attracting immune cells/cytokines to the site of inflammation. Our results provide new insight into the physiological function of MUC8 and enhance our understanding of mucin overproduction during airway inflammation.</P>
김영옥 ( Young Ock Kim ),김호철 ( Ho Cheol Kim ),유영법 ( Young Beob Yu ),이상희 ( Sang Hee Lee ),정선경 ( Sun Kyoung Jeong ),권영신 ( Young Shin Kwon ),강난주 ( Nan Ju Kang ),부영민 ( Yung Min Boo ) 대한본초학회 2003 大韓本草學會誌 Vol.18 No.1
N/A The non-mature antlers of deer, Cervi Parvum Cornu (CPC), have been used as a tonic in traditional Korean medicine. Objectives: The purpose of this study was to evaluate the quality of Cervi Parvum Cornu which is newly processed by lyophiliztion. We compared lyophilized CPC (LCPC) with parboiled CPC (PCPC) by the yield of water extract, the contents of total free amino acids and the patterns of gangliosides. Methods: We analyzed the quantitiative and qualitative determinations of amino acids in LCPC using HPLC method. The contents and patterns of gangliosides in LCPC were measured by gravimetric analysis and HPTLC. Results: The yields of the water extract from LCPC and PCPC gave 18% and 10%, respectively. The contents of total free amino acids in the PCPC were much higher than the LCPC. Comparing the TLC pattern of gangliosides, the both samples showed similar patterns as the purchased gangliosides. The contents of gangliosides in the LCPC (18.6 mg/g) were higher than those in the PCPC (14.3 mg/g). Conclusions: These results suggest that the lyophilizing process may be an alternative method for improving the quality of CPC.
Effects of Dopamine.HCI on Structural Parameters of Bovine Brain Membranes
Bae, Moon-Kyoung,Huh, Min-Hoi,Lee, Seung-Woo,Kang, Hyun-Gu,Pyun, Jae-Ho,Kwak, Myeong-Hee,Jang, Hye-Ock,Yun, Il The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.6
Fluorescence probes located in different membrane regions were used to evaluate the effect of dopamine$.$HCI on the structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and thickness of the lipid bilayer) of synaptosomal plasma membrane vesicles (SPMV), which were obtained from the bovine cerebral cortex. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, and radiationless energy transfer from the tryptophan of membrane pro-teins to Py-3-Py and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS) was also utilized. Dopamine$.$HCI increased both the bulk lateral mobility and annular lipid fluidity, and it had a greater fluidizing effect on the inner monolayer than on the outer monolayer. Furthermore, the drug had a clustering effect on membrane proteins.