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991.
992.
Cyclic mechanical stress (CMS) leads to alterations of cellular functions in the trabecular meshwork (TM), including the up-regulation of transforming growth factor beta 1 (TGFβ1), that can potentially contribute to the pathogenesis of glaucoma. Although microRNAs (miRNAs) are known to play important roles in many biological functions, little is known about their potential involvement in the cellular responses elicited by mechanical stress. Here we analyzed changes in miRNA expression induced by CMS, and examined the possible role of miR-24 in the response of human TM cells to CMS. CMS induced the expression of miR-24 that led to the down regulation of the subtilisin-like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1. FURIN was confirmed as a novel target of miR-24 by 3' UTR luciferase assay and western blot. Overexpression of miR-24 resulted in a significant decrease in activated TGFβ1. This effect was mimicked by down regulation of FURIN by siRNA. Conversely, inhibition of miR-24 expression with a specific antagomir led to a small but significant increase in TGFβ1. Furthermore, the increase in active TGFβ1 induced by CMS in HTM cells was prevented by miR-24. Altogether, our results suggest that miRNAs might contribute to the regulation of responses to CMS in TM cells. Specifically, miR-24 might play an important role in modulating the induction of TGFβ1 mediated by CMS through direct targeting of FURIN. 相似文献
993.
Xu J Yang Y Qiu G Lal G Yin N Wu Z Bromberg JS Ding Y 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(11):6597-6606
Th17 play a central role in autoimmune inflammatory responses. Th1 are also necessary for autoimmune disease development. The interplay of Th1 signals and how they coordinate with Th17 during inflammatory disease pathogenesis are incompletely understood. In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and colitis induction. We showed that in the absence of the strong Th2 mediator Stat6, neither Stat4 nor T-bet is required for IFN-γ production and Th1 development. However, addition of Stat4 deficiency abolished colitis induced by Stat6/T-bet double-knockout cells, despite Th1 and Th17 responses. The failure of colitis induction by Stat4/Stat6/T-bet triple-knockout cells is largely due to elevated Foxp3(+) regulatory T cell (Treg) development. These results highlight the critical role of Stat4 Th1 signals in autoimmune responses in suppressing Foxp3(+) Treg responses and altering the balance between Th17 and Tregs to favor autoimmune disease. 相似文献
994.
Effects of ammonium on the photosynthetic recovery of Nostoc flagelliforme Berk. et M. A. Curtis were assayed when being rehydrated in low‐K+ or high‐K+ medium. Its photosynthetic recovery was K+ limited after 3 years of dry storage. The potassium absorption of N. flagelliforme reached the maximum after 3 h rehydration in low‐K+ medium but at 5 min in high‐K+ medium. The K+ content of N. flagelliforme rehydrated in high‐K+ medium was much higher than that in low‐K+ medium. The maximal PSII quantum yield (Fv/Fm) value of N. flagelliforme decreased significantly when samples were rehydrated in low‐K+ medium treated with 5 mM NH4Cl. However, the treatment of 20 mM NH4Cl had little effect on its Fv/Fm value in high‐K+ medium. The relative Fv/Fm 24 h EC50 (concentration at which 50% inhibition occurred) value of NH4+ in high‐K+ medium (64.35 mM) was much higher than that in low‐K+ medium (22.17 mM). This finding indicated that high K+ could alleviate the inhibitory action of NH4+ upon the photosynthetic recovery of N. flagelliforme during rehydration. In the presence of 10 mM tetraethylammonium chloride (TEACl), the relative Fv/Fm 24 h EC50 value of NH4+ was increased to 46.34 and 70.78 mM, respectively, in low‐K+ and high‐K+ media. This observation suggested that NH4+ entered into N. flagelliforme cells via the K+ channel. Furthermore, NH4+ could decrease K+ absorption in high‐K+ medium. 相似文献
995.
996.
Adler A Park YD Larsen P Nagarajan V Wollenberg K Qiu J Myers TG Williamson PR 《The Journal of biological chemistry》2011,286(23):20977-20990
997.
Cao JY Qiu S Zhang J Wang JJ Zhang XM Luo JH 《The Journal of biological chemistry》2011,286(31):27698-27705
N-Methyl-D-aspartate receptors (NMDARs), one of three main classes of ionotropic glutamate receptors, play major roles in synaptic plasticity, synaptogenesis, and excitotoxicity. Unlike non-NMDA receptors, NMDARs are thought to comprise obligatory heterotetrameric complexes mainly composed of GluN1 and GluN2 subunits. When expressed alone in heterogenous cells, such as HEK293 cells, most of the NMDAR subunits can neither leave the endoplasmic reticulum (ER) nor be expressed in the cell membrane because of the ER retention signals. Only when NMDARs are heteromerically assembled can the ER retention signals be masked and NMDARs be expressed in the surface membrane. However, the mechanisms underlying NMDAR assembly remain poorly understood. To identify regions in subunits that mediate this assembly, we made a series of truncated or chimeric cDNA constructs. Using FRET measurement in living cells combined with immunostaining and coimmunoprecipitation analysis, we examined the assembly-determining domains of NMDAR subunits. Our results indicate that the transmembrane region of subunits is necessary for the assembly of NMDAR subunits, both for the homodimer and the heteromer. 相似文献
998.
Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways 总被引:5,自引:0,他引:5
Qiu X 《Prostaglandins, leukotrienes, and essential fatty acids》2003,68(2):181-186
Docosahexaenoic acid (DHA) has long been recognized for its beneficial effect in humans, but its biosynthetic pathway has not been clearly established until recently. According to Sprecher, in mammals, DHA is synthesized via a retro-conversion process in peroxisomes-the aerobic delta4 desaturation-independent pathway. Recent identification of a Thraustochytrium delta4 desaturase indicates that delta4 desaturation is indeed involved in DHA synthesis in Thraustochytrium. More interestingly, an alternative pathway for DHA biosynthesis-the anaerobic polyketide synthase pathway was also reported recently to occur in Schizochytrium, another member of the Thraustochytriidae. This mini-review attempts to assess the latest research on these distinct pathways for DHA biosynthesis. 相似文献
999.
Zhu YF Wang XC Connors P Wilcoxen K Gao Y Gross R Strack N Gross T McCarthy JR Xie Q Ling N Chen C 《Bioorganic & medicinal chemistry letters》2003,13(11):1931-1934
4-benzylquinolines 5, based on a series of isoquinolines 1, were prepared and tested as inhibitors of the IGF/IGFBP-3 complex based on their ability to displace IGF-I from its binding to IGF-binding protein-3. SAR studies on the 6,7-dihydroxy moiety of the quinoline 5a showed that the catecol moiety could be replaced with other functional groups. Computational modeling of the 5a/mini-IGFBP-5 complex revealed the possible binding site of 5a on IGFBP-5. 相似文献
1000.
1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI) 总被引:4,自引:0,他引:4
Heerding DA Chan G DeWolf WE Fosberry AP Janson CA Jaworski DD McManus E Miller WH Moore TD Payne DJ Qiu X Rittenhouse SF Slater-Radosti C Smith W Takata DT Vaidya KS Yuan CC Huffman WF 《Bioorganic & medicinal chemistry letters》2001,11(16):2061-2065
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI. 相似文献