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11.
Émilie Degagné Jade Degrandmaison Djordje M. Grbic Valérie Vinette Guillaume Arguin Fernand‐Pierre Gendron 《Journal of cellular physiology》2013,228(1):99-109
P2Y2 receptor expression is increased in intestinal epithelial cells (IECs) during inflammatory bowel diseases (IBDs). In this context, P2Y2 stimulates PGE2 release by IECs, suggesting a role in wound healing. For this study, we have used the non‐cancerous IEC‐6 cell line. IEC‐6 cell migration was determined using Boyden chambers and the single‐edged razor blade model of wounding. The receptor was activated using ATP, UTP, or 2‐thioUTP. Pharmacological inhibitors, a blocking peptide, a neutralizing antibody and interfering RNAs were used to characterize the signaling events. Focal adhesions and microtubule (MT) dynamics were determined by immunofluorescence using anti‐vinculin and anti‐acetylated‐α‐tubulin antibodies, respectively. In vivo, the dextran sodium sulfate mouse model of colitis was used to characterize the effects of P2Y2 agonist 2‐thioUTP on remission. We showed that P2Y2 increased cell migration and wound closure by recruiting Go protein with the cooperation of integrin αv. Following P2Y2 activation, we demonstrated that GSK3β activity was inhibited in response to Akt activation. This leads to MT stabilization and increased number of focal adhesions. In vivo, P2Y2 activation stimulates remission, as illustrated by a reduction in the disease activity index values and histological scores as compared to control mice. These findings highlight a novel function for this receptor in IECs. They also illustrate that P2Y receptors could be targeted for the development of innovative therapies for the treatment of IBDs. J. Cell. Physiol. 228: 99–109, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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Matthew A. Benson Helen Batchelor Surawee Chuaiphichai Jade Bailey Hanneng Zhu Dennis J. Stuehr Shoumo Bhattacharya Keith M. Channon Mark J. Crabtree 《The Journal of biological chemistry》2013,288(41):29836-29845
Tetrahydrobiopterin (BH4) is a required cofactor for the synthesis of NO by NOS. Bioavailability of BH4 is a critical factor in regulating the balance between NO and superoxide production by endothelial NOS (eNOS coupling). Crystal structures of the mouse inducible NOS oxygenase domain reveal a homologous BH4-binding site located in the dimer interface and a conserved tryptophan residue that engages in hydrogen bonding or aromatic stacking interactions with the BH4 ring. The role of this residue in eNOS coupling remains unexplored. We overexpressed human eNOS W447A and W447F mutants in novel cell lines with tetracycline-regulated expression of human GTP cyclohydrolase I, the rate-limiting enzyme in BH4 synthesis, to determine the importance of BH4 and Trp-447 in eNOS uncoupling. NO production was abolished in eNOS-W447A cells and diminished in cells expressing W447F, despite high BH4 levels. eNOS-derived superoxide production was significantly elevated in W447A and W447F versus wild-type eNOS, and this was sufficient to oxidize BH4 to 7,8-dihydrobiopterin. In uncoupled, BH4-deficient cells, the deleterious effects of W447A mutation were greatly exacerbated, resulting in further attenuation of NO and greatly increased superoxide production. eNOS dimerization was attenuated in W447A eNOS cells and further reduced in BH4-deficient cells, as demonstrated using a novel split Renilla luciferase biosensor. Reduction of cellular BH4 levels resulted in a switch from an eNOS dimer to an eNOS monomer. These data reveal a key role for Trp-447 in determining NO versus superoxide production by eNOS, by effects on BH4-dependent catalysis, and by modulating eNOS dimer formation. 相似文献
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Jeremy Gross Ian J. Passmore Jade C. S. Chung Olena Rzhepishevska Madeleine Ramstedt Martin Welch 《生物学前沿》2013,8(4):387-394
The opportunistic pathogen Pseudomonas aeruginosa commonly causes chronic and ultimately deadly lung infections in individuals with the genetic disease cystic fibrosis (CF). P. aeruginosa is metabolically diverse; it displays a remarkable ability to adapt to and successfully occupy almost any niche, including the ecologically complex CF lung. These P. aeruginosa lung infections are a fascinating example of microbial evolution within a “natural” ecosystem. Initially, P. aeruginosa shares the lung niche with a plethora of other microorganisms and is vulnerable to antibiotic challenges. Over time, adaptive evolution leads to certain commonly-observed phenotypic changes within the P. aeruginosa population, some of which render it resistant to antibiotics and apparently help it to out-compete the other species that co-habit the airways. Improving genomics techniques continue to elucidate the evolutionary mechanisms of P. aeruginosa within the CF lung and will hopefully identify new vulnerabilities in this robust and versatile pathogen. 相似文献
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The parasphenoid is located in the cranium of many vertebrates. When present, it is always an unpaired, dermal bone. While most basal vertebrates have a parasphenoid, most placental mammals lack this element and have an unpaired, dermal vomer in a similar position (i.e. associated with the same bones) and with a similar function. As such, the parasphenoid and the vomer were considered homologous by some early twentieth century researchers. However, others questioned this homology based on comparisons between mammals and reptiles. Here we investigate the parasphenoid bone across the major vertebrate lineages (amphibians, reptiles, mammals and teleosts) including both developmental and evolutionary aspects, which until now have not been considered together. We find that within all the major vertebrate lineages there are organisms that possess a parasphenoid and a vomer, while the parasphenoid is absent within caecilians and most placental mammals. Based on our assessment and Patterson's conjunction tests, we conclude that the non‐mammalian parasphenoid and the vomer in mammals cannot be considered homologous. Additionally, the parasphenoid is likely homologous between sarcopterygian and actinopterygian lineages. This research attempts to resolve the issue of the parasphenoid homology and highlights where gaps in our knowledge are still present. 相似文献
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Simon P. Fletcher Daniel J. Chin Lore Gruenbaum Hans Bitter Erik Rasmussen Palanikumar Ravindran David C. Swinney Fabian Birzele Roland Schmucki Stefan H. Lorenz Erhard Kopetzki Jade Carter Miriam Triyatni Linta M. Thampi Junming Yang Dalal AlDeghaither Marta G. Murreddu Paul Cote Stephan Menne 《PLoS pathogens》2016,12(3)
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Yeung Jade Jugé Lauriane Hatt Alice Bilston Lynne E. 《Biomechanics and modeling in mechanobiology》2019,18(5):1497-1505
Biomechanics and Modeling in Mechanobiology - The aim of this study is to characterise the stiffness of white and grey matter in paediatric subjects using magnetic resonance elastography (MRE) and... 相似文献