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排序方式: 共有475条查询结果,搜索用时 265 毫秒
31.
Anderson CL Iyer SS Ziegler TR Jones DP 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(3):R1069-R1075
Human cell lines regulate the redox state (E(h)) of the cysteine/cystine (Cys/CySS) couple in culture medium to approximately -80 mV, a value similar to the average E(h) for Cys/CySS in human plasma. The mechanisms involved in regulation of extracellular E(h) of Cys/CySS are not known, but GSH is released from tissues at rates proportional to tissue GSH concentration, and this released GSH could react with CySS to contribute to maintenance of this balance. The present study was undertaken to determine whether depletion of cellular GSH alters regulation of extracellular Cys/CySS E(h). Decrease of GSH in HT-29 cells by inhibiting synthesis with l-buthionine-[S,R]-sulfoximine showed no effect on the rate of reduction of extracellular CySS to achieve a stable E(h) for Cys/CySS in the culture medium. Limiting Cys and CySS in the culture medium also substantially decreased cellular GSH but resulted in no significant effect on extracellular Cys/CySS E(h). Addition of CySS to these cells showed that extracellular Cys/CySS E(h) approached -80 mV at 4 h while cellular GSH and extracellular GSH/GSSG E(h) recovered more slowly. Together, these results show that HT-29 cells have the capacity to regulate the extracellular Cys/CySS E(h) by mechanisms that are independent of cellular GSH. The results suggest that transport systems for Cys and CySS and/or membranal oxidoreductases could be more important than cellular GSH in regulation of extracellular Cys/CySS E(h). 相似文献
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Xu J Woods CR Mora AL Joodi R Brigham KL Iyer S Rojas M 《American journal of physiology. Lung cellular and molecular physiology》2007,293(1):L131-L141
Bone marrow-derived mesenchymal stem cells (BMDMSCs) appear to be important in repair of the chronic lung injury caused by bleomycin in mice. To determine effects of these BMDMSCs on an acute inflammatory response, we injected C57BL/6 mice intraperitoneally with 1 mg/kg endotoxin followed either by intravenous infusion of 5 x 10(5) BMDMSCs, the same number of lung fibroblasts, or an equal volume of normal saline solution. Lungs harvested 6, 24, and 48 h and 14 days after endotoxin showed that BMDMSC administration prevented endotoxin-induced lung inflammation, injury, and edema. Although we were able to detect donor cells in the lungs at 1 day after endotoxin, by 14 days no donor cells were detected. BMDMSC administration suppressed the endotoxin-induced increase in circulating proinflammatory cytokines without decreasing circulating levels of anti-inflammatory mediators. Ex vivo cocultures of BMDMSC and lung cells from endotoxemic animals demonstrated a bilateral conversation in which lung cells stimulated proliferation and migration of stem cells and suppressed proinflammatory cytokine production by lung cells. We conclude that BMDMSCs decrease both the systemic and local inflammatory responses induced by endotoxin. These effects do not require either lung engraftment or differentiation of the stem cells and are due at least in part to the production of stem cell chemoattractants by the lungs and to humoral and physical interactions between stem cells and lung cells. We speculate that mobilization of this population of BMDMSCs may be a general mechanism for modulating an acute inflammatory response. 相似文献
34.
Glia maturation factor (GMF), a highly conserved brain-specific protein, isolated, sequenced and cloned in our laboratory.
Overexpression of GMF in astrocytes induces the production and secretion of granulocyte-macrophage-colony stimulating factor
(GM-CSF), and subsequent immune activation of microglia, expression of several proinflammatory genes including major histocompatibility
complex proteins, IL-1β, and MIP-1β, all associated with the development of experimental autoimmune encephalomyelitis (EAE),
the animal model for multiple sclerosis. Based on GMF’s ability to activate microglia and induce well-established proinflammatory
mediators, including GM-CSF, we hypothesize that GMF is involved in the pathogenesis of inflammatory disease EAE. In this
present investigation, using GMF-deficient mice, we study the role of GMF and how the lack of GMF affects the EAE disease.
Our results show a significant decrease in incidence, delay in onset, and reduced severity of EAE in GMF-deficient mice, and
support the hypothesis that GMF plays a major role in the pathogenesis of disease. 相似文献
35.
Diatoms constitute an important component of the fouling community. Although a lot of work has dealt with the fouling diatom community structure, work on the species interactions within the community is still meagre. In this regard, a study was carried out by transferring natural diatom biofilms into controlled conditions in order to understand the roles of nutrients, initial cell inoculum and seasonal variation in species composition in structuring the fouling diatom community. This community exhibited seasonal variation during the monsoon, post-monsoon and pre-monsoon periods. During each of these seasons, diatom species interactions varied depending upon the species composition. It was observed that excess nutrients favoured those species with comparatively higher growth rates, thereby suppressing the growth of other co-existing species. This competitive trait was found to be effective at an appropriate cell density ratio of the competitive and target species. Understanding such pathways will be useful for modelling the interactions between diatom species in various habitats under different resource conditions. 相似文献
36.
Smita Salian-Mehta Mei Xu Timothy A. McKinsey Stuart Tobet Margaret E. Wierman 《The Journal of biological chemistry》2015,290(22):14045-14056
The impact of histone deacetylases (HDACs) in the control of gonadotropin releasing hormone (GnRH) neuronal development is unknown. We identified an increase in many HDACs in GT1-7 (differentiated) compared with NLT (undifferentiated) GnRH neuronal cell lines. Increased HDAC9 mRNA and protein and specific deacetylase activity in GT1-7 cells suggested a functional role. Introduction of HDAC9 in NLT cells protected from serum withdrawal induced apoptosis and impaired basal neuronal cell movement. Conversely, silencing of endogenous HDAC9 in GT1-7 cells increased apoptosis and cell movement. Comparison of WT and mutant HDAC9 constructs demonstrated that the HDAC9 pro-survival effects required combined cytoplasmic and nuclear localization, whereas the effects on cell movement required a cytoplasmic site of action. Co-immunoprecipitation demonstrated a novel interaction of HDAC9 selectively with the Class IIb HDAC6. HDAC6 was also up-regulated at the mRNA and protein levels, and HDAC6 catalytic activity was significantly increased in GT1-7 compared with NLT cells. HDAC9 interacted with HDAC6 through its second catalytic domain. Silencing of HDAC6, HDAC9, or both, in GT1-7 cells augmented apoptosis compared with controls. HDAC6 and -9 had additive effects to promote cell survival via modulating the BAX/BCL2 pathway. Silencing of HDAC6 resulted in an activation of movement of GT1-7 cells with induction in acetylation of α-tubulin. Inhibition of HDAC6 and HDAC9 together resulted in an additive effect to increase cell movement but did not alter the acetylation of αtubulin. Together, these studies identify a novel interaction of Class IIa HDAC9 with Class IIb HDAC6 to modulate cell movement and survival in GnRH neurons. 相似文献
37.
Christian P. Craddock Nicolette Adams Fiona M. Bryant Smita Kurup Peter J. Eastmond 《The Plant cell》2015,27(4):1251-1264
Regulation of membrane lipid biosynthesis is critical for cell function. We previously reported that disruption of PHOSPHATIDIC ACID PHOSPHOHYDROLASE1 (PAH1) and PAH2 stimulates net phosphatidylcholine (PC) biosynthesis and proliferation of the endoplasmic reticulum (ER) in Arabidopsis thaliana. Here, we show that this response is caused specifically by a reduction in the catalytic activity of the protein and positively correlates with an accumulation of its substrate, phosphatidic acid (PA). The accumulation of PC in pah1 pah2 is suppressed by disruption of CTP:PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE1 (CCT1), which encodes a key enzyme in the nucleotide pathway for PC biosynthesis. The activity of recombinant CCT1 is stimulated by lipid vesicles containing PA. Truncation of CCT1, to remove the predicted C-terminal amphipathic lipid binding domain, produced a constitutively active enzyme. Overexpression of native CCT1 in Arabidopsis has no significant effect on PC biosynthesis or ER morphology, but overexpression of the truncated constitutively active version largely replicates the pah1 pah2 phenotype. Our data establish that membrane homeostasis is regulated by lipid composition in Arabidopsis and reveal a mechanism through which the abundance of PA, mediated by PAH activity, modulates CCT activity to govern PC content. 相似文献
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Best T Li D Skol AD Kirchhoff T Jackson SA Yasui Y Bhatia S Strong LC Domchek SM Nathanson KL Olopade OI Huang RS Mack TM Conti DV Offit K Cozen W Robison LL Onel K 《Nature medicine》2011,17(8):941-943
Survivors of pediatric Hodgkin's lymphoma are at risk for radiation therapy-induced second malignant neoplasms (SMNs). We identified two variants at chromosome 6q21 associated with SMNs in survivors of Hodgkin's lymphoma treated with radiation therapy as children but not as adults. The variants comprise a risk locus associated with decreased basal expression of PRDM1 (encoding PR domain containing 1, with ZNF domain) and impaired induction of the PRDM1 protein after radiation exposure. These data suggest a new gene-exposure interaction that may implicate PRDM1 in the etiology of radiation therapy-induced SMNs. 相似文献