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931.
Alteration of the tumor microenvironment by aberrant stromal cells influences many aspects of cell biology, including differentiation of stem cells and tumor metastasis. The role of transforming growth factor (TGF)-β signaling in stromal cells of the tissue microenvironment is critical to both pathways. We examined murine marrow stromal cells with deletion of Smad3 and found that they have an altered cell cycle profile, with a higher fraction of cells in G2/M phase. Deletion of Smad3 significantly abrogates TGF-β signaling and suppresses phosphorylation of CDC27–anaphase-promoting complex (APC) during mitosis, thereby resulting in elevated cyclin-dependent kinase (CDK)1 activity via increased levels of cyclin B. Enhanced CDK1 activity due to deregulation of APC leads in turn to hyperphosphorylation of separase, impeding chromatid separation. A residue Ser1126Ala mutation in separase specifically abolished separase hyperphosphorylation in Smad3-deficient cells. The present results unveil a new function for the TGF-β pathway in the regulation of APC to mediate chromatid separation during mitosis. 相似文献
932.
Zhao Feng Peng Minghui Jessica Chen Yann Wan Yap Jayapal Manikandan Alirio J Melendez Meng Shyan Choy Philip K Moore Nam Sang Cheung 《Nitric oxide》2008,18(2):136-145
Nitric oxide (NO), ubiquitously expressed in the central nervous system, has been perceived to be a potential neuromodulator. Employing cultured murine primary cortical neurons, NO resulted in an inhibition of the ubiquitin-proteasome system (UPS) with a dose- and time-dependent decrease in cell viability. This is consistent with a previous study that reported a dysfunction of UPS with consequential apoptotic death in macrophage cell with NO treatment. However, it cannot be unclear if the drop in UPS efficiency is directly imposed on by NO. Therefore by using microarray analysis, our study revealed an early down-regulation or non-significant differential expression of genes encoding UPS proteins in NOC-18 (NO donor)-treated neurons as compared to an observed elevation of corresponding gene expression genes in lactacystin (classical proteasome inhibitor)-treated neurons (conducted earlier). Furthermore, time-course analysis of proteasome activity in NOC-18-treated neurons demonstrated a late onset of reduction. This is intriguing as it is well established that in an exclusive proteasome dysfunction-induced cell death, a compensatory feedback mechanism will be activated with an initial and concerted up-regulation of genes encoding proteins involved in UPS as seen when neurons were treated with lactacystin. Thus, it is highly suggestive that NO-triggered neuronal death takes on a different signaling cascade from that of a classical proteasome inhibitor, and that the late reduction of proteasome activity is a downstream event following the activation of apoptotic cellular signaling cascade. In intracellular condition, the proteasome is not NO preferred primary target responsible for the trigger of the cell death machinery. In conclusion, we presented novel findings that shed light into NO-induced cell death signaling cascade, which would be important in understanding the pathogenesis of neurodegenerative disorders such as Parkinson's disease. 相似文献
933.
Molecular cloning and characterization of three sigma glutathione S-transferases from disk abalone (Haliotis discus discus) 总被引:1,自引:0,他引:1
Wan Q Whang I Lee J 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2008,151(3):257-267
Three novel glutathione S-transferase (GSTs) cDNAs were cloned from a disk abalone (Haliotis dicus discus) cDNA library. Multiple alignment and phylogenetic analysis of three GSTs revealed that their closest relationship is with insect sigma GSTs. Recombinant GSTs were over-expressed in Escherichia coli as soluble fusion proteins. HdGSTS1 and HdGSTS2 were active towards 1-chloro-2,4-dinitrobenzene and ethacrynic acid, whereas HdGSTS3 appeared to be a non-enzymatic GST. Two active GSTs had similar optimum conditions for enzymatic reaction at pH 8.0 and temperature of approximately 30 degrees C. Molecular modeling analysis of three GSTs implicates their diverse active sites as being responsible for their different enzymatic features. Three sigma GSTs had significantly different expression patterns and levels of expression in abalone tissues, indicating their different functions. After 48 h-exposure to three model marine pollutants, only HdGSTS1 exhibited a proper inducibility, exhibiting its good biomarker potential for organic contaminants in marine environment. In contrast, the other two sigma GSTs revealed a minor role in the response of pollutants exposure. 相似文献
934.
Jong Wan Bae Seunghee Shin S. Mohan Raj Song Eun Lee Sun-Gu Lee Yong-Joo Jeong Sunghoon Park 《Biotechnology and Bioprocess Engineering》2008,13(1):69-76
A recombinant Escherichia coli (pBAB1) containing styrene monooxygenase (SMO) was developed for the conversion of styrene to enantiopure (S)-styrene oxide that is an important chiral building block in organic synthesis. The styAB genes encoding SMO was cloned into a multicopy plasmid under the tightly regulated promoter of bacterial l-arabinose operon which is inducible by l-arabinose. The recombinant showed that expression level of StyA protein and whole-cell SMO activities were varied depending
on the concentration of the inducer l-arabinose. The maximum SMO activity was 108 U/g cdw when the cells were induced with 0.2% l-arabinose. SDS-PAGE and Western blot analyses indicated that whole-cell SMO activity was strongly correlated with the expression
level of StyA protein. Organic-aqueous two-phase experiment could yield 50 mM enantiopure (S)-styrene oxide in organic phase in 18 h, but the recombinant SMO activity was unstable during the reaction. The expression
of styAB under the control of l-arabinose promoter was significantly repressed in the presence of glucose. 相似文献
935.
Joon Ki Hong Jung Eun Hwang Woo Sik Chung Kyun Oh Lee Young Ju Choi Sang Wan Gal Beom -Seok Park Chae Oh Lim 《Journal of Plant Biology》2008,51(5):347-353
Phytocystatins are plant cysteine proteinase inhibitors that regulate endogenous and heterologous cysteine proteinases of
the papain family. A cDNA encoding the phytocystatin BrCYS1 (Brassica rapa cysteine proteinase inhibitor 1 ) has been isolated from Chinese cabbage (B. rapa subsp.pekinensis) flower buds. In order to explore the role of this inhibitory enzyme, tobacco plants (Nicotiana tabacum L. cv. Samson) containing altered amounts of phytocystatin were generated by over-expressingBrCYS1 cDNA in either the sense or the antisense configuration. The resulting plants hadin vitro enzyme inhibitory activities that were over 10% of those detected in wild type plants. The transgenic plants exhibited retarded
seed germination and seedling growth and a reduced seed yield, whereas these properties were enhanced in antisense plants.
These data suggest that BrCYS1 participates in the control of seed germination, post-germination and plant growth by regulating
cysteine peptidase activity. 相似文献
936.
937.
Background
Kinases are under extensive investigation as targets for drug development. Discovering novel kinases whose inhibition induces cancer-cell-selective lethality would be of value. Recent advances in RNA interference have enabled the realization of this goal. 相似文献938.
Wah Heng Lee Christopher W Wong Wan Yee Leong Lance D Miller Wing Kin Sung 《BMC bioinformatics》2008,9(1):368
Background
Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. 相似文献939.
Shen Q Li X Qiu Y Su M Liu Y Li H Wang X Zou X Yan C Yu L Li S Wan C He L Jia W 《Journal of proteome research》2008,7(5):2151-2157
Epidemiology and studies in animal models have revealed that prenatal malnutrition is highly correlated with abnormal fetal neurodevelopment. We present here a combined metabonomic and metallomic profiling technique to associate the metabolic and trace-elemental composition variations of rat amniotic fluid (AF) in malnourished pregnant rats with the retardation of fetal rat neurodevelopment. The AF samples from three groups of pregnant Sprague-Dawley rats, which were fed either a normal diet, a low-protein diet, or "a famine diet", were subjected to GC/MS and ICP/MS combined with multivariate data analysis (MVDA). PCA scores plot of both GC/MS and ICP/MS data showed similar and unique metabolic signatures of AF in response to the different diets. Rats in the famine group released increased amounts of glycine, inositol, putrescine, and rubidium and decreased amounts of methionine, dopa, tryptophan, glutamine, zinc, cobalt, and selenium in the AF. These discriminable variations in the AF may indicate the abnormality of a number of metabolic pathways in fetal rats including the folate cycle and methionine pathway, the monoamine pathway, and tri-iodothyronine (T3) metabolism. The abnormalities may be the result of metabolites or elemental differences or a combination of both. This study demonstrates the potential of combining profiling of small-molecule metabolites and trace elements to broaden the understanding of biological variations associated with fetal neurodevelopment induced by environmental perturbation. 相似文献
940.
It is well known that the steroid hormone glucocorticoid and its nuclear receptor regulate the inflammatory process, a crucial component in the pathophysiological process related to human diseases that include atherosclerosis, obesity and type II diabetes, inflammatory bowel disease, Alzheimer's disease, multiple sclerosis, and liver tumors. Growing evidence demonstrates that orphan and adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors, liver x receptors, the farnesoid x receptor, NR4As, retinoid x receptors, and the pregnane x receptor, regulate the inflammatory and metabolic profiles in a ligand-dependent or -independent manner in human and animal models. This review summarizes the regulatory roles of these nuclear receptors in the inflammatory process and the underlying mechanisms. 相似文献