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( So Ri Kim ),( Yong Chul Lee ),( Dong Im Kim ),( Yang Keun Rhee ),( Heung Bum Lee ),( Seoung Ju Park ),( Chi Ryang Chung ),( Seung Yong Park ),( Mi Ran Kang ) 대한결핵 및 호흡기학회 2012 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.114 No.-
Oxidative stress is well known to be implicated in the development of asthma. The mitochondrial respiratory chain is a major site of intracellular reactive oxygen species (ROS) generation and, at the same time, an important target for the damaging effects of ROS. Mito-Tempo is a specific mitochondrial ROS inhibitor and it is known to be associated with opening of mi-tochondrial permeability transition pore and inhibition of cell necroptosis or apoptosis. However, there is little information on the protective effects of Mito-Tempo on the inflammatory airway disorders including bronchial asthma and its acute exacerbation. We investigate the effects of Mito-tempo on the allergic airway inflammation and hyperresponsiveness using the mice sensitized with OVA and LPS and then challenged with OVA (OVALPS-OVA mice). The OVALPS-OVA mice showed the typical features of neutrophilic asthma; increased airway inflammatory cells, the pathologic changes, the increased levels of Th2 cytokines in lungs of OVALPS-OVA mice, increased mitochondrial ROS generation, and increased bronchial hyperresponsiveness. Interestingly, we found that in OVALPS-OVA mice, Mito-Tempo, a novel mitochondrial targeting agent significantly reduced the increases in inflammatory cytokines, mitochondrial ROS generation, airway inflammation, and bron-chial hyperresponsiveness. These findings indicate that mitochondrial dysfunction including oxidative damage may be im-plicated in the pathogenesis of bronchial asthma and provide the therapeutic potential of a mitochondrial targeting agent, Mito-Tempo, for bronchial asthma.
Park, Hye-Seo,Kim, Eun-Hee,Sung, Yoon-Hui,Kang, Mi-Ran,Chung, In-Kwon,Cheong, Chae-Joon,Lee, Weon-Tae Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.4
The ability of protoberberine alkaloids, berberine and berberrubine, to act as topoisomerase II poisons is linked to the anti-cancer activity. Minor alterations in structure have a significant effect on their relative activity. Berberine, which has methoxy group at the 19-position, is significantly less potent than berberrubine. Several observations support non-specific binding to HP14 by the berberine: (i) nonspecific upfield changes in $^1H$ chemical shift for protons of the berberine; (ii) the broadening of imino protons of HP14 upon binding of the berberine; (iii) very small increases in duplex melting temperature in the presence of the berberine. Our results reveal that substitution of a hydroxyl group to a methoxy group on the 19-position, thereby converting the berberrubine to the berberine is associated with a non-specific DNA binding affinity and a reduced topoisomerase II poisoning. The presence of a bulky 19-methoxy substituent decreases intercalating properties of berberine and makes it inactive as topoisomerase II poison.
Park, Hye-Seo,Kim, Eun-Hee,Kang, Mi-Ran,Chung, In-Kwon,Cheong, Chae-Joon,Lee, Weon-Tae Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.10
The topoisomerase II poisoning effect of certain protoberberine alkaloids is associated with anti-cancer activity. Structure-activity relationships of protoberberine analogues substituted on the ring protons reveal that substitution at the C19 position is an important determinant of biological activity. In this study, the effects of substituent modification at the C19 position on the interaction of protoberberines with DNA are determined using UV and NMR spectroscopy. The line broadening effect on aliphatic resonances, chemical shift changes of the imino protons of HP14 upon berberine and berberrubine binding to HP14, and the rate of the exchange process between protoberberine analogs bound indicate that berberrubine binds HP14 more specifically than berberine. In addition, the free HP14 is altered by the substituent at the 19-position. UV spectra of berberrubine have shown a hypochromic effect together with a slight red shift, which are usually regarded as characteristics of DNA intercalation. These results are consistent with our previous report that the berberrubine is partially intercalated with HP14 with molar ratio 1 : 1, whereas a non-specific interaction is predominant between the berberine and HP14.
( Mi Ran Jo ),( Mi Hee Park ),( Dong Young Choi ),( Dong Yeun Yuk ),( Yuk Mo Lee ),( Jin Moo Lee ),( Jae Hwang Jeong ),( Ki Wan Oh ),( Moon Soon Lee ),( Sang Bae Han ),( Jin Tae Hong ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.3
Amyloid beta (Aβ)-induced neurotoxicity is a major pathological mechanism of Alzheimer`s disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on Aβ1-42-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited Aβ1-42-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa- B. L-theanine also significantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50 μg/ml) concomitantly attenuated Aβ1-42 (5 μM)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on Aβ-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.
Park, Ju-Mi,Jeon, Hye-Ran,Pang, Eun-Kyoung,Kim, Myung-Rae,Kang, Na-Ra Korean Academy of Periodontology 2008 Journal of Periodontal & Implant Science Vol.38 No.2
Purpose: The aim of this study was to evaluate adhesion and gene expression of the MC3T3-E1 cells cultured on machined titanium surface (MS) and anodized titanium surface (AS) using MTT test, Scanning electron micrograph and cDNA microarray. Materials and Methods: The MTT test assay was used for examining the proliferation of MC3T3-E1 cells, osteoblast like cells from Rat calvaria, on MS and AS for 24 hours and 48 hours. Cell cultures were incubated for 24 hours to evaluate the influence of the substrate geometry on both surfaces using a Scanning Electron Micrograph (SEM). The cDNA microarray Agilent Rat 22K chip was used to monitor expressions of genes. Results: After 24 hours of adhesion, the cell density on AS was higher than MS (p < 0.05). After 48 hours the cell density on both titanium surfaces were similar (p > 0.05). AS had the irregular, rough and porous surface texture. After 48 hours incubation of the MC3T3-E1 cells, connective tissue growth factor (CTGF) was up-regulated on AS than MS (more than 2 fold) and the insulin-like growth factor 1 receptor was down-regulated (more than 2 fold) on AS than MS. Conclusion: Microarray assay at 48 hours after culturing the cells on both surfaces revealed that osteoinductive molecules appeared more prominent on AS, whereas the adhesion molecules on the biomaterial were higher on MS than AS, which will affect the phenotype of the plated cells depending on the surface morphology.