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排序方式: 共有604条查询结果,搜索用时 15 毫秒
61.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
62.
Lopes M Goupille O Saint Cloment C Lallemand Y Cumano A Robert B 《Development (Cambridge, England)》2011,138(14):3055-3066
Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs. 相似文献
63.
Cassano M Dellavalle A Tedesco FS Quattrocelli M Crippa S Ronzoni F Salvade A Berardi E Torrente Y Cossu G Sampaolesi M 《Development (Cambridge, England)》2011,138(20):4523-4533
Mice deficient in α-sarcoglycan (Sgca-null mice) develop progressive muscular dystrophy and serve as a model for human limb girdle muscular dystrophy type 2D. Sgca-null mice suffer a more severe myopathy than that of mdx mice, the model for Duchenne muscular dystrophy. This is the opposite of what is observed in humans and the reason for this is unknown. In an attempt to understand the cellular basis of this severe muscular dystrophy, we isolated clonal populations of myogenic progenitor cells (MPCs), the resident postnatal muscle progenitors of dystrophic and wild-type mice. MPCs from Sgca-null mice generated much smaller clones than MPCs from wild-type or mdx dystrophic mice. Impaired proliferation of Sgca-null myogenic precursors was confirmed by single fiber analysis and this difference correlated with Sgca expression during MPC proliferation. In the absence of dystrophin and associated proteins, which are only expressed after differentiation, SGCA complexes with and stabilizes FGFR1. Deficiency of Sgca leads to an absence of FGFR1 expression at the membrane and impaired MPC proliferation in response to bFGF. The low proliferation rate of Sgca-null MPCs was rescued by transduction with Sgca-expressing lentiviral vectors. When transplanted into dystrophic muscle, Sgca-null MPCs exhibited reduced engraftment. The reduced proliferative ability of Sgca-null MPCs explains, at least in part, the severity of this muscular dystrophy and also why wild-type donor progenitor cells engraft efficiently and consequently ameliorate disease. 相似文献
64.
65.
Long-distance flights can cause a number of clinical problems due to mild hypoxia resulting from cabin pressurization. Using a chronobiological approach, the aim of this work was to assess the clinical tolerance and biological impact of daytime exposure to hypobaric hypoxia on markers of iron metabolism and plasma proteins. Fourteen healthy, male volunteers, ages 23 to 39 yrs, spent 8.5 h in a hypobaric chamber (from 07:45 to 16:15 h) simulating an altitude of 8000 ft. This was followed by another 8.5-h session 4 wks later simulating conditions at an altitude of 12,000 ft. Biological variables were assayed every 2 h over two 24-h spans (control and hypoxia spans, respectively) per simulated altitude. Whereas most of the subjects tolerated the 8000 ft exposure well, eight subjects (57%) presented clear clinical signs of hypoxic intolerance at 12,000 ft. The 24-h blood iron profile showed a biphasic pattern at both altitude simulations, with a significant (~40%) increase during hypoxia, followed by a (~25%) decrease during the first hours of recovery. The iron circadian rhythm showed a significant phase delay during the hypoxic exposure at 8000 ft vs. reference. Mean 24-h ferritin levels decreased at both altitudes, but mainly during the nighttime after the 12,000 ft exposure in accordance with Cosinor analysis. The transferrin and total plasma proteins 24-h profiles did not show significant change. Moreover, significant differences, mainly in iron, ferritin, and transferrin, were found at 12,000 ft according to the clinical tolerance to hypoxia, and significant correlations were found between the mid-range crossing times, i.e., here half-descent times (d-T(50)), for ferritin and total plasma proteins and the reported level of clinical discomfort under hypoxia. This study shows that an 8.5-h exposure to mild hypoxia is able to alter very quickly the 24-h pattern of iron and ferritin. These alterations seem to depend, at least in part, on the clinical tolerance to hypoxia and may help explain the interindividual differences observed in the tolerance to hypoxia. 相似文献
66.
67.
Mateescu B Batista L Cardon M Gruosso T de Feraudy Y Mariani O Nicolas A Meyniel JP Cottu P Sastre-Garau X Mechta-Grigoriou F 《Nature medicine》2011,17(12):1627-1635
Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials. 相似文献
68.
Francisco J Azuaje Haiying Wang Huiru Zheng Frédérique Léonard Magali Rolland-Turner Lu Zhang Yvan Devaux Daniel R Wagner 《BMC systems biology》2011,5(1):46
Background
Endothelial progenitor cells (EPCs) have been implicated in different processes crucial to vasculature repair, which may offer the basis for new therapeutic strategies in cardiovascular disease. Despite advances facilitated by functional genomics, there is a lack of systems-level understanding of treatment response mechanisms of EPCs. In this research we aimed to characterize the EPCs response to adenosine (Ado), a cardioprotective factor, based on the systems-level integration of gene expression data and prior functional knowledge. Specifically, we set out to identify novel biosignatures of Ado-treatment response in EPCs. 相似文献69.
Cadmium-113 nuclear magnetic resonance (113Cd nmr) was used to elucidate the structural properties of the cadmium binding sites in human liver metallothionein. The isotopically labeled 113Cd-metallothionein was prepared by the in vitro exchange of the native metals (greater than 94% zinc) for 113CdCl2 during isolation. The two isoproteins, MT-1 and MT-2, showed 113Cd nmr resonances in the chemical shift range 610–670 ppm. The multiplet structure of the resonances is due to two bond scalar interactions between adjacent 113Cd ions linked by cysteine thiolate ligands. Homonuclear 113Cd decoupling experiments allowed the determination of the metal cluster structure, which, similar to the rabbit liver metallothionein, consists of a four- and a three-metal cluster designated cluster A and cluster B, respectively. Chemical shift similarities in the 113Cd nmr spectra of the human, rabbit and calf liver MT-1 and MT-2 are observed, especially for cluster A. Small variations in chemical shifts are explained in terms of differences in the primary structure between the two human isoproteins. 相似文献
70.
Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights. 相似文献