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841.
Shin-Young Park Ju Hwan Cho Weina Ma Hye-Jin Choi Joong-Soo Han 《Cellular signalling》2010,22(4):619-628
The purpose of this study was to identify the role of phospholipase D2 (PLD2) in lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis. LPS enhanced NO synthesis and inducible nitric oxide synthase (iNOS) expression in macrophage cell line, Raw 264.7 cells. When Raw 264.7 cells were stimulated with LPS, the expressions of PLDs were increased. Thus, to investigate the role of PLD in NO synthesis, we transfected PLD1, PLD2, and their dominant negative forms to Raw 264.7 cells, respectively. Interestingly, only PLD2 overexpression, but not that of PLD1, increased NO synthesis and iNOS expression. Moreover, LPS-induced NO synthesis and iNOS expression were blocked by PLD2 siRNA, suggesting that LPS upregulates NO synthesis through PLD2. Next, we investigated the S6K1-p42/44 MAPK-STAT3 signaling pathway in LPS-induced NO synthesis mechanism. Knockdown of PLD2 with siRNA also decreased phosphorylation of S6K1, p42/44 MAPK and STAT3 induced by LPS. Furthermore, we found that STAT3 bound with the iNOS promoter, and their binding was mediated by PLD2. Taken together, our results demonstrate the importance of PLD2 for LPS-induced NO synthesis in Raw 264.7 cells with involvement of the S6K1-p42/44 MAPK-STAT3 pathway. 相似文献
842.
Hyun-Jeong Kwak Kyoung-Mi Park Hye-Eun Choi Hyun-Joung Lim Jin-Hee Park Hyun-Young Park 《Cellular signalling》2010,22(1):80-87
Zileuton has been demonstrated to act as an anti-inflammatory agent by virtue of its well-known ability to inhibit 5-lipoxygenase (5-LO). However, the effects of zileuton on cardiovascular disease and cardiomyocyte apoptosis are unclear. Here, we investigated the effects of zileuton on apoptosis of cardiac myogenic H9c2 cells and neonatal rat cardiomyocytes (NRCMs), and examined the possible role of PKCδ-mediated induction of COX-2 in these effects. Treatment of H9c2 cells with zileuton efficiently induced COX-2 expression and PGE2 biosynthesis in a time- and dose-dependent manner. Zileuton also exerted a profound protective effect against H2O2-induced oxidative stress, a mimic of reperfusion damage in vitro, and this protective effect was abolished by COX-2-selective inhibitor. When we investigated the signalling pathways involved in zileuton-induced COX-2 expression, we found that zileuton acts as a PKCδ activator, causing it to translocate from the cytosol to nucleus. Inhibition of PKCδ activation with rottlerlin, a PKCδ-specific inhibitor, abolished the zileuton-induced protection against H2O2-induced cell death and inhibited zileuton-induced COX-2 expression and PGE2 production. The protective effect of zileuton was dramatically diminished by treatment with LY294002 or PD98059. Furthermore, zileuton-stimulated ERK1/2 and Akt phosphorylation was attenuated by rottlerin, indicating that PKCδ might act upstream of ERK1/2 and Akt. Moreover, inhibition of either ERK1/2 or Akt activation abolished zileuton-induced COX-2 expression. Knockdown of PKCδ with siRNA also reversed the protective effect of zileuton and blocked the induction of COX-2. These results suggest that zileuton-induced COX-2 expression is sequentially mediated through PKCδ-dependent activation of ERK1/2 and Akt. Based on these findings, we propose that zileuton might provide a new therapeutic strategy for ischemia/reperfusion injury of the heart. 相似文献
843.
Jung Woong Choi Seyoung Lim Yong-Seok Oh Eung-Kyun Kim Sun-Hee Kim Yun-Hee Kim Kyun Heo Jaeyoon Kim Jung Kuk Kim Yong Ryul Yang Sung Ho Ryu Pann-Ghill Suh 《Cellular signalling》2010,22(7):1153-1161
Among phospholipase C (PLC) isozymes (β, γ, δ, ε, ζ and η), PLC-β plays a key role in G-protein coupled receptor (GPCR)-mediated signaling. PLC-β subtypes are often overlapped in their distribution, but have unique knock-out phenotypes in organism, suggesting that each subtype may have the different role even within the same type of cells. In this study, we examined the possibility of the differential coupling of each PLC-β subtype to GPCRs, and explored the molecular mechanism underlying the specificity. Firstly, we found that PLC-β1 and PLC-β3 are activated by bradykinin (BK) or lysophosphatidic acid (LPA), respectively. BK-triggered phosphoinositides hydrolysis and subsequent Ca2+ mobilization were abolished specifically by PLC-β1 silencing, whereas LPA-triggered events were by PLC-β3 silencing. Secondly, we showed the evidence that PDZ scaffold proteins is a key mediator for the selective coupling between PLC-β subtype and GPCR. We found PAR-3 mediates physical interaction between PLC-β1 and BK receptor, while NHERF2 does between PLC-β3 and LPA2 receptor. Consistently, the silencing of PAR-3 or NHERF2 blunted PLC signaling induced by BK or LPA respectively. Taken together, these data suggest that each subtype of PLC-β is selectively coupled to GPCR via PDZ scaffold proteins in given cell types and plays differential role in the signaling of various GPCRs. 相似文献
844.
Sul OJ Kim JC Kyung TW Kim HJ Kim YY Kim SH Kim JS Choi HS 《Bioscience, biotechnology, and biochemistry》2010,74(11):2209-2213
Gold nanoparticles inhibited osteoclast (OC) formation induced by the receptor activator of nuclear factor-κB ligand (RANKL) in bone marrow-derived macrophages (BMMs). This was accompanied by a decreased level of tartrate-resistant alkaline phosphatase (TRAP) and less activation of nuclear factor (NF)-κB. The nanoparticles also reduced the production of reactive oxygen species (ROS) in response to RANKL and upregulated RANKL-induced glutathione peroxidase-1 (Gpx-1), suggesting a role as an antioxidant in the BMM. The inhibitory effects on OC formation might have been due to elevated defense against oxidative stress. 相似文献
845.
A novel approach CE-Ploc is proposed for predicting protein subcellular locations by exploiting diversity both in feature and decision spaces. The
diversity in a sequence of feature spaces is exploited using hydrophobicity and hydrophilicity of amphiphilic pseudo amino
acid composition and a specific learning mechanism. Diversity in learning mechanisms is exploited by fusion of classifiers
that are based on different learning mechanisms. Significant improvement in prediction performance is observed using jackknife
and independent dataset tests. 相似文献
846.
847.
Won Il Choi Kwang-Sik Choi Dong-Pyeo Lyu Jung-Su Lee Jongok Lim Seunghwan Lee Sang-Chul Shin Yeong-Jin Chung Young-Seuk Park 《Biodiversity and Conservation》2010,19(8):2291-2305
Fauna assemblages reflect their habitat relating to ecological function in an ecosystem. The functional groups are concerned
with how a resource is processed by different species to provide a specific ecosystem service or function. We elucidated seasonal
changes of coleopteran functional groups in forests, and evaluated their ecological roles related to available food resources.
Coleopteran communities were collected weekly or biweekly using Malaise traps at nine study sites in Japanese red pine forests
in Korea from late June to September 2005. Compositions of the functional groups were compared at the different sites and
at sampling times with respect to taxa richness and abundance. Cluster analysis and non-metric multidimensional scaling were
used to characterize spatial and temporal changes of functional groups. Herbivores and dead/live wood feeders regulating primary
production in the pine forests were the dominant coleopteran groups in July, followed by detritivores and predators that dominated
from July to August, resulting from the accumulation of detritus. Then, fungivores became dominant due to increased fungal
biomass in the forest. Seasonal changes of coleopteran functional groups shifted from regulators of primary production to
regulators of decomposition, reflecting their available food resources. In addition, abundance of detritivores and predators
were dependent on total abundance of coleopterans, suggesting that these two groups reflect their habitat condition. 相似文献
848.
849.
Young Ae Yoon Chan Sun Park Myung Hun Cha Hyunho Choi Jae Young Sim Jae Gyu Kim 《Bioorganic & medicinal chemistry letters》2010,20(19):5735-5738
A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H+/K+ ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a potent APA with H+/K+ ATPase, IC50 = 52 nM. 相似文献
850.
Arjun Basnet Pritam Thapa Radha Karki Hoyoung Choi Jae Hun Choi Minho Yun Byeong-Seon Jeong Yurngdong Jahng Younghwa Na Won-Jea Cho Youngjoo Kwon Chong-Soon Lee Eung-Seok Lee 《Bioorganic & medicinal chemistry letters》2010,20(1):42-47
For the development of novel antitumor agents, 2,6-dithienyl-4-furyl pyridine derivatives were prepared and evaluated for their topoisomerase I and II inhibitory activity as well as cytotoxicity against several human cancer cell lines. Among the 21 prepared compounds, compound 24 exhibited strong topoisomerase I inhibitory activity. In addition, a docking study with topoisomerase I and compound 24 was performed. 相似文献